Variant Classifier

Interactive tool for genetic variant classification based on ACMG guidelines

Step 1 of 11

Current Criteria

Basic Information *

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Basic Information

Enter the variant details and associated condition for classification analysis. Required fields must be completed before proceeding.

Variant *

Variant

Enter the genetic variant in standard format (e.g., c.123A>G, p.Met1Leu, chr1:12345A>G). Ensure accuracy for proper classification.

Disease/Condition *

Disease/Condition

Specify the disease or condition associated with the variant (e.g., Hypertrophic cardiomyopathy).

Zygosity

Indicates whether the variant is present on one or both copies of the chromosome.

Heterozygous Homozygous Hemizygous

Inheritance Pattern

The pattern of inheritance for the associated disease/condition.

Autosomal Dominant Autosomal Recessive X-linked Dominant X-linked Recessive

Is the gene associated with the mentioned condition with the single etiology?

Gene Association

Check if the gene is known to cause the specified disease.

Yes No Not Known

Variant Characterization *

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Variant Characterization

Determine the variant type and its predicted impact on protein function.

Is this a null variant?

Null Variant

Variants causing loss of function: nonsense, frameshift, canonical splice sites (±1/±2), initiation codon loss, single/multi-exon deletions.

Nonsense, frameshift, canonical ±1/±2 splice, initiation codon loss, single/multi-exon deletion

Yes, this is a null variant No, this is not a null variant Not Known

Is this a missense variant?

Missense Variant

A variant that changes one amino acid to another (e.g., p.Arg123Gln).

Yes, this is a missense variant No, this is not a missense variant Not Known

Is this a novel missense variant?

Novel Missense

A missense variant not previously reported in literature or databases.

Yes, this is novel No, this has been reported before Not Known

Has the same amino-acid change been reported earlier regardless of nucleotide change? (e.g., Val→Leu caused by G>C or G>T).

Same Amino Acid Change

Has the same amino acid change been reported, regardless of nucleotide change

Yes, same amino acid change reported No, amino acid change not reported Not Known

Is there a different amino-acid substitution at the same residue where a pathogenic variant is already known?

Different AA at Same Residue

A different amino acid substitution at the same residue where a pathogenic variant is known

Yes, different pathogenic variant at same position No, no known pathogenic variant at this position Not Known

Is missense a known mechanism for this disorder?

Missense Mechanism

Is missense mutation an established mechanism of disease for this disorder?

Yes, missense is established mechanism No, missense is not established mechanism Not Known

Is there an alternative molecular basis for this disorder?

Alternative Molecular Basis

Are there other known genetic mechanisms causing this disorder besides variants in this gene?

Yes No Not Known

Is there an alternative molecular basis for this disorder?

Alternative Molecular Basis (Non-Missense)

Are there other known genetic mechanisms causing this disorder besides variants in this gene?

Yes No Not Known

Segregation Analysis *

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Segregation Analysis

Analyze how the variant segregates within families and its consistency with inheritance patterns.

🔗 OMIM Database 🔗 gnomAD 🔗 TOPMed

Have you done segregation analysis?

Segregation Analysis

Family studies to determine if the variant segregates with disease in affected family members.

Yes, segregation analysis completed No, segregation analysis not done Not Known

Observed segregation result

Segregation Result

How does the variant segregates in the family.

Variant absent in both parents Variant present in one or both parents Variant present in both parents Variant present in only mother Not Known

Is the variant assumed to be de novo?

De Novo Variant

A variant present in the proband but absent in both parents (assuming confirmed maternity and paternity).

Yes, assumed de novo No, not de novo Not Known

Functional Analysis *

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Functional Analysis

Evaluate in vitro or in vivo studies on the variant's effect on protein function.

🔗 OMIM Database 🔗 gnomAD 🔗 TOPMed

Has the variant been studied functionally?

Functional Studies

In vitro or in vivo studies demonstrating the effect of the variant on protein function.

Population Frequency *

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Population Frequency

Evaluate the frequency of the variant in healthy population databases.

🔗 OMIM Database 🔗 gnomAD 🔗 TOPMed

Is the frequency of variant <1% of healthy population?

Population Frequency

Check allele frequency in databases like gnomAD.

Is allele frequency ≥5%?

High Allele Frequency

Stand-alone benign if allele frequency is ≥5%.

Yes No Not Known

Variant Position *

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Variant Position

Determine if the variant is in a known functional region or mutational hotspot.

Is this variant in a mutational hotspot or well-established functional domain?

Hotspot/Domain

Critical region where mutations are known to cause disease.

Yes No Not Known

Cis/Trans *

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Cis/Trans

Evaluate the phase relationship with other variants.

Is the variant present in trans with an additional pathogenic/likely pathogenic variant?

In Trans

Is the variant on the opposite chromosome to another pathogenic variant?

Yes No Not Known

Variant Effect *

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Variant Effect

Assess the predicted effect on protein structure or length.

Does this variant lead to deletions/insertions/stop-loss?

Protein Length Changes

In-frame insertions/deletions or stop-loss variants.

Yes No Not Known

Is this in a repetitive region?

Repetitive Region

Low complexity regions prone to sequencing artifacts.

Yes No Not Known

In Silico Predictions *

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In Silico Predictions

Computational predictions of the variant's effect using tools like SIFT, PolyPhen, etc.

🔗 VarSome 🔗 Franklin 🔗 dbNSFP

What does the silico tools say about the variant?

In Silico Tools

Predictions from tools like SIFT, PolyPhen, etc.

Reputable Source *

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Reputable Source

Check classification in reputable databases like ClinVar or HGMD.

🔗 PubMed (Search Gene name and nucleotide change)

Is the variant reported as pathogenic in a reputable source?

Reputable Source

Classification in databases like ClinVar, HGMD.

Synonymous Variant *

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Synonymous Variant

Evaluate if the variant is silent and does not affect splicing.

Is the variant synonymous with no predicted impact on splicing?

Synonymous Variant

Silent variant not affecting splicing.

Yes No Not Known

Final Classification

Calculating Classification...

Pathogenic Evidence

Very Strong (PVS):	0
Strong (PS):	0
Moderate (PM):	0
Supporting (PP):	0

Total Score: 0

Pathogenic Strength: 0

Benign Evidence

Stand alone (BA):	0
Strong (BS):	0
Supporting (BP):	0

Benign Strength: 0

Applied Criteria

Resources & References

External databases and tools for further variant analysis

Variant Classifier

Current Criteria

Basic Information * i Basic Information Enter the variant details and associated condition for classification analysis. Required fields must be completed before proceeding.

Variant Characterization * i Variant Characterization Determine the variant type and its predicted impact on protein function.

Segregation Analysis * i Segregation Analysis Analyze how the variant segregates within families and its consistency with inheritance patterns.

Functional Analysis * i Functional Analysis Evaluate in vitro or in vivo studies on the variant's effect on protein function.

Population Frequency * i Population Frequency Evaluate the frequency of the variant in healthy population databases.

Variant Position * i Variant Position Determine if the variant is in a known functional region or mutational hotspot.

Cis/Trans * i Cis/Trans Evaluate the phase relationship with other variants.

Variant Effect * i Variant Effect Assess the predicted effect on protein structure or length.

In Silico Predictions * i In Silico Predictions Computational predictions of the variant's effect using tools like SIFT, PolyPhen, etc.

Reputable Source * i Reputable Source Check classification in reputable databases like ClinVar or HGMD.

Synonymous Variant * i Synonymous Variant Evaluate if the variant is silent and does not affect splicing.

Final Classification

Pathogenic Evidence

Benign Evidence

Applied Criteria

Resources & References

Population Databases

Disease Databases

In Silico Prediction Tools

Literature Search

Basic Information *

i

Basic Information

Enter the variant details and associated condition for classification analysis. Required fields must be completed before proceeding.

Variant Characterization *

i

Variant Characterization

Determine the variant type and its predicted impact on protein function.

Segregation Analysis *

i

Segregation Analysis

Analyze how the variant segregates within families and its consistency with inheritance patterns.

Functional Analysis *

i

Functional Analysis

Evaluate in vitro or in vivo studies on the variant's effect on protein function.

Population Frequency *

i

Population Frequency

Evaluate the frequency of the variant in healthy population databases.

Variant Position *

i

Variant Position

Determine if the variant is in a known functional region or mutational hotspot.

Cis/Trans *

i

Cis/Trans

Evaluate the phase relationship with other variants.

Variant Effect *

i

Variant Effect

Assess the predicted effect on protein structure or length.

In Silico Predictions *

i

In Silico Predictions

Computational predictions of the variant's effect using tools like SIFT, PolyPhen, etc.

Reputable Source *

i

Reputable Source

Check classification in reputable databases like ClinVar or HGMD.

Synonymous Variant *

i

Synonymous Variant

Evaluate if the variant is silent and does not affect splicing.