Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665969 | SCV000790190 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2017-03-08 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001855449 | SCV002291679 | likely pathogenic | not provided | 2024-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 206 of the MYO7A protein (p.Arg206Cys). This variant is present in population databases (rs782361954, gnomAD 0.02%). This missense change has been observed in individual(s) with autosomal dominant deafness (PMID: 32428919). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 551019). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. 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. |
| Genomic Medicine Center of Excellence, |
RCV003989576 | SCV004806916 | likely pathogenic | Usher syndrome type 1 | 2024-03-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004702281 | SCV005205220 | uncertain significance | not specified | 2024-06-14 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.616C>T (p.Arg206Cys) results in a non-conservative amino acid change located in the Myosin head, motor domain (IPR001609) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 249168 control chromosomes. c.616C>T has been reported in the literature in heterozygous individuals affected with autosomal dominant nonsyndromic hearing loss, in a setting of multi-gene panel testing showing segregation with disease in one family or in a setting of single-gene testing in a proband with an unaffected heterozygous mother (e.g. Su_2009, Lu_2020). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32428919, 19299023). ClinVar contains an entry for this variant (Variation ID: 551019). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |