ClinVar Miner

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

dbSNP: rs782279338
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
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 genetic hearing loss 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 Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-11-17 criteria provided, single submitter clinical testing
Invitae RCV001067075 SCV001232108 pathogenic not provided 2022-09-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function. ClinVar contains an entry for this variant (Variation ID: 555138). This missense change has been observed in individual(s) with autosomal recessive hearing loss (PMID: 23770805, 27573290). It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 395 of the MYO7A protein (p.Arg395Cys).
Fulgent Genetics, Fulgent Genetics RCV002485553 SCV002796468 likely pathogenic Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2021-09-13 criteria provided, single submitter clinical testing
University of Washington Center for Mendelian Genomics, University of Washington RCV001291468 SCV001479972 likely pathogenic Hearing loss, autosomal recessive no assertion criteria provided research
Natera, Inc. RCV001829868 SCV002086569 likely pathogenic Usher syndrome type 1B 2020-10-14 no assertion criteria provided clinical testing

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.