Variant: NM_000260.4(MYO7A):c.1183C>T (p.Arg395Cys)

CA6197402

555138 (ClinVar)

Gene: MYO7A

Condition: nonsyndromic genetic deafness

Inheritance Mode: Autosomal recessive inheritance

UUID: 55512a59-1ed0-41e4-80d2-be897c90cfe6

HGVS expressions

NM_000260.4:c.1183C>T
NM_000260.4(MYO7A):c.1183C>T (p.Arg395Cys)
NM_000260.3:c.1183C>T
NM_001127179.2:c.1183C>T
NM_001127180.1:c.1183C>T
NM_001127180.2:c.1183C>T
NM_001369365.1:c.1150C>T
ENST00000409619.6:c.1150C>T
ENST00000409709.7:c.1183C>T
ENST00000409893.5:c.1183C>T
ENST00000458637.6:c.1183C>T
ENST00000620575.4:c.1183C>T
NC_000011.10:g.77160265C>T
CM000673.2:g.77160265C>T
NC_000011.9:g.76871311C>T
CM000673.1:g.76871311C>T
NC_000011.8:g.76548959C>T
NG_009086.1:g.37002C>T
NG_009086.2:g.37020C>T

Likely Pathogenic

• Met criteria codes: PM2_Supporting PP1_Strong PM3_Supporting PP3

• Not Met criteria codes: PP4

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The c.1183C>T (p.Arg395Cys) variant in MYO7A was identified in 0.0085% (2/23608) of South Asian alleles in gnomAD v2 (PM2_Supporting). This variant has been detected in 2 patients with hearing loss. One patient had profound prelingual sensorineural hearing loss while the other had progressive severe hearing loss. For both of these probands the variant was observed in a homozygous state (PM3_Supporting, PMIDs: 23770805, 27573290). The variant has been reported to segregate with disease in at least 3 affected family members (PP1_Strong, PMID: 23770805). The REVEL computational prediction tool produced a score of 0.773, which is above the threshold necessary to apply PP3. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss. There was not sufficient evidence to determine if this variant is causative for Usher syndrome or nonsyndromic hearing loss. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PP1_Strong, PM2_Supporting, PM3_Supporting, PP3.

Met criteria codes

• PM2_Supporting: Present in 0.0085% (2/23608) of South Asian chromosomes in gnomAD v2.1.1 and not present in gnomAD v3.
• PP1_Strong: 7 affected individuals with variant segregating in a consanguineous family in Naz et al and 3 segregations in a consanguineous family in Shahzad et al.
• PM3_Supporting: Total of 0.5 points.
• PP3: Conserved across all mammals and vertebrates except yellowbelly pufferfish (Tyrosine). REVEL score is 0.773.

Not Met criteria codes

• PP4: No ophthalmologic testing performed on Shahzad family and Naz family was specifically noted to not have RP

Approved on: 2020-10-20

Published on: 2020-10-20