Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001807903 | SCV002058167 | uncertain significance | Usher syndrome type 1 | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MYO7A related disorder (PMID:32747562, PS1_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000016, PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (3CNET: 0.901, PP3_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. |
| King Laboratory, |
RCV001807902 | SCV002059926 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 2 | 2020-08-01 | criteria provided, single submitter | research | MYO7A c.2683C>T, p.R895C is a non-conservative change in a highly conserved residue of MYO7A. The variant is homozygous in 3 Palestinian children with severe to profound pre-lingual hearing loss (Abu Rayyan 2020). The variant is absent from 1300 Palestinian controls and present in 4/246366 alleles on gnomAD, all heterozygotes. |
| Labcorp Genetics |
RCV001885285 | SCV002201389 | uncertain significance | not provided | 2022-08-09 | 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 895 of the MYO7A protein (p.Arg895Cys). This variant is present in population databases (rs781916427, gnomAD 0.003%). This missense change has been observed in individual(s) with MYO7A-related conditions (PMID: 32747562). ClinVar contains an entry for this variant (Variation ID: 1333215). 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 not expected to disrupt MYO7A protein function. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235600 | SCV003934402 | uncertain significance | not specified | 2023-05-04 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.2683C>T (p.Arg895Cys) results in a non-conservative amino acid change in 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 1.6e-05 in 246366 control chromosomes (gnomAD). c.2683C>T has been reported in the literature in an individual affected with hearing loss (example: Rayyan_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 publication have been ascertained in the context of this evaluation (PMID: 32747562). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |