Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036132 | SCV000059784 | likely pathogenic | Rare genetic deafness | 2013-11-18 | criteria provided, single submitter | clinical testing | The His133Tyr variant in MYO7A has been reported in three individuals with Usher syndrome (Le Guedard-Mereuze 2010, Roux 2011, LMM unpublished data), and was no t identified in large population studies. All three individuals were compound he terozygous for a second pathogenic MYO7A variant. In addition, computational ana lyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, an d SIFT) suggest that the variant may impact the protein. In summary, the His133T yr variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significance. |
| Labcorp Genetics |
RCV001852746 | SCV002238506 | pathogenic | not provided | 2023-07-25 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with Usher syndrome (PMID: 20052763, 33576163). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 133 of the MYO7A protein (p.His133Tyr). ClinVar contains an entry for this variant (Variation ID: 43228). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.His133 amino acid residue in MYO7A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23770805). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |
| Fulgent Genetics, |
RCV002482971 | SCV002794234 | likely pathogenic | Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2024-02-08 | criteria provided, single submitter | clinical testing | |
| Genomic Medicine Center of Excellence, |
RCV003987336 | SCV004804709 | pathogenic | Usher syndrome type 1 | 2024-03-17 | criteria provided, single submitter | research | |
| Institute of Human Genetics, |
RCV004814943 | SCV005073383 | pathogenic | Retinal dystrophy | 2009-01-01 | criteria provided, single submitter | clinical testing |