Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668444 | SCV000793049 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2017-08-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001378983 | SCV001576696 | pathogenic | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 163 of the MYO7A protein (p.Gly163Arg). This variant is present in population databases (no rsID available, gnomAD 0.004%). This missense change has been observed in individual(s) with autosomal recessive Usher syndrome and autosomal recessive deafness (PMID: 16679490, 21873662, 26561413, 27583663, 31479088). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 553070). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001378983 | SCV003798521 | pathogenic | not provided | 2022-08-17 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32864763, 27583663, 31479088, 26561413, 16679490, 26969326, 21436283, 33089500, 21873662) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235337 | SCV003934403 | pathogenic | Usher syndrome | 2023-05-12 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.487G>A (p.Gly163Arg) 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 4e-06 in 249206 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.487G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Usher Syndrome (e.g., Roux_2006, Atik_2015, Bouzidi_2022). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 26561413, 35551639, 21436283). Five ClinVar submitters (evaluation after 2014) have cited the variant, and all laboratories classified the variant as pathogenic (n = 3) or likely pathogenic (n = 2). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Institute of Human Genetics, |
RCV004794433 | SCV005072164 | likely pathogenic | Retinal dystrophy | 2021-01-01 | criteria provided, single submitter | clinical testing | |
| Ophthalmic Genetics Group, |
RCV004794433 | SCV005415514 | pathogenic | Retinal dystrophy | 2024-05-27 | criteria provided, single submitter | research | |
| Natera, |
RCV001835089 | SCV002093119 | likely pathogenic | Usher syndrome type 1B | 2020-01-21 | no assertion criteria provided | clinical testing | |
| Department of Biotechnology and Genetic Engineering, |
RCV003106015 | SCV002600102 | pathogenic | Usher syndrome type 1 | 2022-08-22 | no assertion criteria provided | research |