ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1997G>A (p.Arg666Gln) (rs782396605)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001171540 SCV001334325 uncertain significance Usher syndrome 2020-05-20 reviewed by expert panel curation The c.1997G>A (p.Arg666Gln) variant in MYO7A is present in 10/42046 (0.012% CI 95%) of African alleles in gnomAD v3, which is a low enough frequency to award PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive Usher syndrome (PM2_Supporting). This variant has been detected in 1 proband with Usher syndrome, however, they carried another VUS with phase unknown (PM3_Supporting not met; ClinVar ID: 196099; PMIDs: 27460420, 31479088). The REVEL computational prediction analysis tool produced a score of 0.841, which is above the threshold necessary to apply PP3. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_Supporting, PP3.
Counsyl RCV000672944 SCV000798101 uncertain significance Deafness, autosomal recessive 2; Usher syndrome type 1 2018-02-28 criteria provided, single submitter clinical testing
Mendelics RCV000988605 SCV001138384 likely pathogenic Usher syndrome type 1 2020-04-24 criteria provided, single submitter clinical testing
Invitae RCV001309116 SCV001498602 uncertain significance not provided 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 666 of the MYO7A protein (p.Arg666Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs782396605, ExAC 0.01%). This variant has been observed in individual(s) with clinical features of Usher syndrome (PMID: 27460420, 31479088, 27344577). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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.