Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036200 | SCV000059852 | pathogenic | Rare genetic deafness | 2014-08-15 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
| Counsyl | RCV000669133 | SCV000793849 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2017-09-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001223334 | SCV001395477 | pathogenic | not provided | 2024-04-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1887 of the MYO7A protein (p.Pro1887Leu). 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 missense change has been observed in individuals with autosomal recessive MYO7A-related conditions (PMID: 10930322, 24194196, 25468891). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 43295). 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. |
| Ocular Genomics Institute, |
RCV001376326 | SCV001573434 | pathogenic | Usher syndrome type 1 | 2021-04-08 | criteria provided, single submitter | research | The MYO7A c.5660C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PP1-S, PM3-S. Based on this evidence we have classified this variant as Pathogenic. |
| Revvity Omics, |
RCV001223334 | SCV002017870 | likely pathogenic | not provided | 2019-02-27 | criteria provided, single submitter | clinical testing | |
| 3billion, |
RCV001376326 | SCV002521199 | pathogenic | Usher syndrome type 1 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.92; 3Cnet: 0.84). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000043295). The variant has been reported to co-segregate with the disease in at least 5 similarly affected relatives/individuals in the same family or similarly affected unrelated family (PMID:24194196). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Gene |
RCV001223334 | SCV002546579 | likely pathogenic | not provided | 2022-05-31 | criteria provided, single submitter | clinical testing | Segregates with nonsyndromic hearing loss in multiple affected homozygous individuals from a single family in published literature (Ben-Salem et al., 2014); 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: 26968074, 24194196, 10930322, 25468891, 33111992, 33671976, 30303587) |
| University of Washington Center for Mendelian Genomics, |
RCV001291104 | SCV001479470 | likely pathogenic | Hearing loss, autosomal recessive | no assertion criteria provided | research |