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.4115T>G (p.Val1372Gly)

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Curation History
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CA353603

224749 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 580d30fb-1bb1-468a-bb63-1d786dac0556

Approved on: 2020-04-29

Published on: 2020-04-30

HGVS expressions

NM_000260.4:c.4115T>G

NM_000260.4(MYO7A):c.4115T>G (p.Val1372Gly)

NC_000011.10:g.77192241T>G

CM000673.2:g.77192241T>G

NC_000011.9:g.76903286T>G

CM000673.1:g.76903286T>G

NC_000011.8:g.76580934T>G

NG_009086.1:g.68977T>G

NG_009086.2:g.68996T>G

ENST00000409709.9:c.4115T>G

ENST00000670577.1:c.1956T>G

ENST00000409619.6:c.4082T>G

ENST00000409709.7:c.4115T>G

ENST00000458169.2:c.1658T>G

ENST00000458637.6:c.4115T>G

ENST00000481328.7:n.1658T>G

NM_000260.3:c.4115T>G

NM_001127180.1:c.4115T>G

NM_001127180.2:c.4115T>G

NM_001369365.1:c.4082T>G

Uncertain Significance

PP3 PM3 PM2

PP4

Evidence Links 1

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.4115T>G (p.Val1372Gly) variant in MYO7A is absent from gnomAD (PM2). The REVEL computational prediction analysis tool produced a score of 0.869, which is above the threshold necessary to apply PP3. While this variant was reported with a second loss of function variant in MYO7A in an inherited retinal disease cohort that includes Usher syndrome patients, it was unclear whether the patient with these variants had Usher syndrome or if the variants were in trans (PM3 not met; PMID: 26872967, SCV000259091.1). In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2, PP3.

PP3

The REVEL score is 0.869. MaxEntScan predicts creation of 5' cryptic splice site. Valine residue conserved across all mammals in UCSC browser. An Ile is present at this position in the parrot, scarlet macaw, fugu, pufferfish, and Japanese rice fish.

PM3

One proband with this variant and another pathogenic variant in trans.

PubMed:26872967

PM2

This variant is absent from gnomAD v2.1.1 and gnomAD v3.

PP4

This individual may have hearing loss and retinal disease.

Curation History

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