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.1817G>A (p.Arg606His)

Curation Version - 1.0
Curation History
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CA6197622

517357 (ClinVar)

Gene: MYO7A

Condition: nonsyndromic genetic deafness

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: afa3b665-0c01-40e2-9432-4938ce1c8bff

Approved on: 2023-07-19

Published on: 2023-10-05

HGVS expressions

NM_000260.4:c.1817G>A

NM_000260.4(MYO7A):c.1817G>A (p.Arg606His)

NC_000011.10:g.77172767G>A

CM000673.2:g.77172767G>A

NC_000011.9:g.76883813G>A

CM000673.1:g.76883813G>A

NC_000011.8:g.76561461G>A

NG_009086.1:g.49504G>A

NG_009086.2:g.49522G>A

ENST00000409709.9:c.1817G>A

ENST00000669443.1:c.181G>A

ENST00000409619.6:c.1784G>A

ENST00000409709.7:c.1817G>A

ENST00000409893.5:c.1817G>A

ENST00000458637.6:c.1817G>A

ENST00000620575.4:c.1817G>A

NM_000260.3:c.1817G>A

NM_001127179.2:c.1817G>A

NM_001127180.1:c.1817G>A

NM_001127180.2:c.1817G>A

NM_001369365.1:c.1784G>A

Uncertain Significance

PP3 PM3

PP4 PP1 PP2 PM6 PM2 PM1 PM4 PM5 PVS1 BA1 BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP1 BP4 PS2 PS4 PS3 PS1

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.1817 G>A (NM_000260.4(MYO7A):c.1817G>A (p.Arg606His)) variant in MYO7A is a missense variant predicted to cause substitution of Arginine by Histidine at amino acid 606. The highest major allele frequency in gnomAD v2.1.1 is 0.00035 (0.035 % or 8/23092 alleles) in the South Asian population (PM2_supporting, BS1, and BA1 not met). The computational predictor REVEL gives a score of 0.832, (which is above the threshold of 0.7), evidence that correlates with impact to MYO7A function (PP3). This variant has been detected in at least one individual with autosomal recessive nonsyndromic genetic hearing loss. This proband was compound heterozygous for the variant and a pathogenic variant, confirmed in trans by parental testing (PM3; 1.0 point; LMM Internal Data). The patient with this variant displayed moderate to severe sensorineural hearing loss, although no vision anomalies or difficulty seeing at night were noted (PP4 not met; LMM Internal Data). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive nonsyndromic genetic deafness, based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: (PP3, PM3; Version 2, 7.19.2023).

PP3

The computational predictor REVEL gives a score of 0.832, (which is above the threshold of 0.7, evidence that correlates with impact to MYO7A function (PP3).

PM3

This variant has been detected in at least one individual with autosomal recessive nonsyndromic genetic hearing loss. This proband was compound heterozygous for the variant and a pathogenic variant, confirmed in trans by parental testing (PM3; 1.0 point; LMM Internal Data).

PP4

The patient had congenital progressive moderately severe to severe sensorineural hearing loss and delayed walking. The proband was 16 at time of testing, and had normal eye exam and could see reasonably at night (LMM internal data; PP4 not met).

PP1