Input
Variant type and gene variant profile
PVS1 Predicted null variant in a gene where LOF is a known mechanism of disease. More info...
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PM4 Protein length changing variant. More info...
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PP2 in gene with low rate of benign missense variants and path. missenses common. More info...
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BP1 Missense in gene where only truncating cause disease. More info...
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BP3 In-frame indels in repeat w/out known function. More info...
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Frequency data
PS4 Prevalence in affecteds statistically increased over controls. More info...
More detailed info here........
Apply Apply PS4_M Apply PS4_P Maybe Not applied
PM2 Absent in population databases. More info...
More detailed info here........
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BA1 MAF is too high for disorder. More info...
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BS1 MAF is too high for disorder. More info...
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BS2 Observation in controls inconsistent with disease penetrance. More info...
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Review of literature and databases
PS1 Same amino acid change as an estabilished pathogenic variant. More info...
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PM1 Mutational hot spot or well-studied functional domain without benign variation. More info...
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PM5 Novel missense change at an amino acid residue where a different pathogenic missense change has been seen before. More info...
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PP5 Reputable source reported as pathogenic. More info...
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BP6 Reputable source reported as benign. More info...
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Functional studies
PS3 Well-established functional studies show a deleterious effect. More info...
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BS3 Well-established functional studies show no deleterious effect. More info...
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Computer predictions
PP3 Multiple lines of computational evidence support a deleterious effect on the gene /gene product. More info...
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BP4 Multiple lines of computational evidence suggest no impact on gene /gene product. More info...
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BP7 Silent variant with non predicted splice impact. More info...
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De novo variants
PS2 De novo (paternity and maternity confirmed). More info...
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PM6 De novo (without paternity & maternity confirmed). More info...
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Phenotype and family history information
PP1 Cosegregation with disease in multiple affected family members. More info...
More detailed info here........
Apply PP1 Apply PP1_M Apply PP1_S Maybe Not applied
PP4 Patients phenotype or family history highly specific for gene. More info...
More detailed info here........
Apply Maybe Not applied
BS4 Nonsegregation with disease. More info...
More detailed info here........
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Multiple variants identified in a patient
PM3 For recessive disorders, detected in trans with a pathogenic variant. More info...
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BP2 Observed in cis with a pathogenic variant/ in trans with a dominant variant. More info...
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BP5 Found in case with an alternate cause. More info...
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Apply Maybe Not applied

Summary

VUS (Mixed criteria)

VUS (Criteria not met)

Pathogenic

Likely pathogenic

Likely benign

Benign

Criteria applied:
PVS {{path_vs()}} BA {{benign_a()}}
PS {{path_s()}} BS {{benign_s()}}
PM {{path_m()}} BP {{benign_p()}}
PP {{path_p()}}
Clear