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.3491G>A (p.Arg1164Gln)

Curation Version - 1.1
Curation History
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CA6198071

229012 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7eb4b5cf-80fd-4791-b09c-9e683db74a34

Approved on: 2024-03-28

Published on: 2024-03-28

HGVS expressions

NM_000260.4:c.3491G>A

NM_000260.4(MYO7A):c.3491G>A (p.Arg1164Gln)

NC_000011.10:g.77184703G>A

CM000673.2:g.77184703G>A

NC_000011.9:g.76895748G>A

CM000673.1:g.76895748G>A

NC_000011.8:g.76573396G>A

NG_009086.1:g.61439G>A

NG_009086.2:g.61458G>A

ENST00000409709.9:c.3491G>A

ENST00000409893.6:c.1556G>A

ENST00000670577.1:c.1332G>A

ENST00000409619.6:c.3458G>A

ENST00000409709.7:c.3491G>A

ENST00000409893.5:c.3491G>A

ENST00000458169.2:c.1034G>A

ENST00000458637.6:c.3491G>A

ENST00000467137.1:n.18G>A

ENST00000481328.7:n.1034G>A

ENST00000620575.4:c.3500G>A

NM_000260.3:c.3491G>A

NM_001127179.2:c.3491G>A

NM_001127180.1:c.3491G>A

NM_001127180.2:c.3491G>A

NM_001369365.1:c.3458G>A

Uncertain Significance

PP3 PM2_Supporting

PP4 PM3

Evidence Links 0

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

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Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.3491G>A variant in MYO7A is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 1164 (p.Arg1164Gln). The highest population filtering allele frequency with a confidence interval of 0.95 in gnomAD v4 is 0.00001446 (4/89272 alleles) in the South Asian population, which is lower than the ClinGen Hearing Loss VCEP threshold (≤0.00007) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.935, which is above the threshold of 0.7, evidence that correlates with impact to MYO7A function (PP3). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PM2_P, PP3. (ClinGen Hearing Loss VCEP specifications version 2, 01.17.2024)

PP3

The computational predictor REVEL gives a score of 0.935, which is above the threshold of 0.7, evidence that correlates with impact to MYO7A function (PP3).

PM2_Supporting

The highest population filtering allele frequency with a confidence interval of 0.95 in gnomAD v4 is 0.00001446 (4/89272 alleles) in the South Asian population, which is lower than the ClinGen Hearing Loss VCEP threshold (≤0.00007) for PM2_Supporting, meeting this criterion (PM2_Supporting).

PP4

Not met due to possible alternate cause of RP in proband from LMM.

PM3

LMM reported this variant in 1 individual with hearing loss and RP (SCV000272160.2). The variant was in trans with a second missense variant that was pathogenic/likely pathogenic in ClinVar. NGS indicated that the two MYO7A variants are present in trans configuration. In addition, this individual is reported to have LCHAD, which may explain the RP (Tyni 1998).

Curation History

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