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 - 1.0
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: 2020-03-18

Published on: 2020-03-18

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 PM3 PM2

PP4

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.3491G>A (p.Arg1164Gln) variant in MYO7A was present in 0.003519% (1/28416) of South Asian chromosomes in gnomAD, which is a low enough frequency to apply PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2). This variant was observed in 1 proband with hearing loss and retinitis pigmentosa and another pathogenic variant in MYO7A in trans (PM3; LMM internal data, SCV000272160.2). However, this individual presented with another possible genetic explanation of retinitis pigmentosa (PP4 not met). The REVEL computational prediction analysis tool produced a score of 0.94, which is above the threshold necessary to apply PP3. In summary, the clinical significance of this variant is uncertain based on ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel (PM2, PM3, PP3).

PP3

REVEL score 0.935. Entirely conserved in UCSC. Alamut suggests that this variant may add a cryptic 3' splice site.

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.

PM2

This variant was present in 0.003519% (1/28416) of South Asian alleles in gnomAD v2.1.1 and 0.003097% (2/64578) of European alleles in v3.

PP4

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

Curation History

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