ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1183C>T (p.Arg395Cys) (rs782279338)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001261013 SCV001438400 likely pathogenic Nonsyndromic hearing loss and deafness 2020-10-20 reviewed by expert panel curation 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.
Counsyl RCV000670895 SCV000795808 uncertain significance Deafness, autosomal recessive 2; Usher syndrome type 1 2017-11-17 criteria provided, single submitter clinical testing
Invitae RCV001067075 SCV001232108 likely pathogenic not provided 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 395 of the MYO7A protein (p.Arg395Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to segregate with hearing loss in families (PMID: 23770805, 27573290). ClinVar contains an entry for this variant (Variation ID: 555138). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.