Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000215887 | SCV000271248 | likely pathogenic | Rare genetic deafness | 2015-08-20 | criteria provided, single submitter | clinical testing | The c.2904G>A (p.Glu968Glu) variant in MYO7A has not been previously reported in individuals with hearing loss, but has been identified in 1/8202 East Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg). Although this variant has been seen in the general population, its frequenc y is low enough to be consistent with a recessive carrier frequency. This varian t is located at the last base of the exon, which is a highly conserved nucleotid e that is part of the 5' splice region. Computational tools predict that this v ariant is likely to impact splicing. In addition, a pathogenic variant affectin g the same nucleotide position (c.2904G>T, p.Glu968Asp) has been reported in 7 i ndividuals with Usher syndrome, including one homozygote and five compound heter ozygotes (Bharadwaj 2000, Ouyang 2005, Jacobson 2008, Le Quesne Stabej 2012, Buj akowska 2014, LMM unpublished data). In summary, although additional studies, s uch as functional analysis, are required to fully establish its clinical signifi cance, this variant is likely pathogenic. |
| Labcorp Genetics |
RCV002517524 | SCV003006802 | pathogenic | not provided | 2023-05-21 | criteria provided, single submitter | clinical testing | This variant disrupts the c.2904G nucleotide in the MYO7A gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 10930322, 15660226, 24199935, 25472526, 26969326). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. This sequence change affects codon 968 of the MYO7A mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MYO7A protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs111033233, gnomAD 0.006%). This variant has been observed in individual(s) with clinical features of autosomal recessive MYO7A-related conditions (PMID: 36164746; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 228280). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 23, but is expected to preserve the integrity of the reading-frame (PMID: 36164746). For these reasons, this variant has been classified as Pathogenic. |
| Counsyl | RCV000984198 | SCV001132255 | uncertain significance | Usher syndrome type 1 | 2019-01-24 | no assertion criteria provided | clinical testing | |
| Counsyl | RCV000984287 | SCV001132437 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 2 | 2019-01-24 | no assertion criteria provided | clinical testing |