Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000260.4(MYO7A):c.1208A>G (p.Tyr403Cys)

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Curation History
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CA278736

178667 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6c14c3d8-0f17-4a22-90e6-a7d1b5164306

Approved on: 2019-11-26

Published on: 2019-11-26

HGVS expressions

NM_000260.4:c.1208A>G

NM_000260.4(MYO7A):c.1208A>G (p.Tyr403Cys)

NC_000011.10:g.77160980A>G

CM000673.2:g.77160980A>G

NC_000011.9:g.76872026A>G

CM000673.1:g.76872026A>G

NC_000011.8:g.76549674A>G

NG_009086.1:g.37717A>G

NG_009086.2:g.37735A>G

ENST00000409709.9:c.1208A>G

ENST00000409619.6:c.1175A>G

ENST00000409709.7:c.1208A>G

ENST00000409893.5:c.1208A>G

ENST00000458637.6:c.1208A>G

ENST00000620575.4:c.1208A>G

NM_000260.3:c.1208A>G

NM_001127179.2:c.1208A>G

NM_001127180.1:c.1208A>G

NM_001127180.2:c.1208A>G

NM_001369365.1:c.1175A>G

Likely Pathogenic

PP1 PP3 PP4 PM3 PM2

Evidence Links 0

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.1208A>G (p.Tyr403Cys) variant in MYO7A is present in 0.0064% (1/15398) of non-Finnish European alleles in gnomAD (PM2). This variant has been identified in trans with a second suspected-pathogenic variant (VCV000164724.1) in one proband with profound hearing loss and retinitis pigmentosa, clinical features of Usher syndrome (PM3; PP4; SCV000205114.4). The variant also segregated in one affected family member (PP1; SCV000205114.4). The REVEL computational prediction analysis tool produced a score of 0.941, which is above the threshold necessary to apply PP3. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel (PM2, PP3, PM3, PP4).

PP1

1 segregation in a family affected with profound hearing loss and retinitis pigmentosa who carried another variant (VCV000164724.1) in trans (SCV000199631.4).

PP3

REVEL: .941

PP4

2 affected siblings with profound hearing loss and retinitis pigmentosa who carried another variant (VCV000164724.1) in trans (SCV000199631.4).

PM3

2 affected siblings with profound hearing loss and retinitis pigmentosa who carried another variant (VCV000164724.1) in trans (SCV000199631.4).

PM2

Present in .0064% (1/15398) of European non-Finnish alleles in gnomAD

Curation History

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