Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000622429 | SCV000741117 | pathogenic | Inborn genetic diseases | 2015-12-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001852752 | SCV002245669 | pathogenic | not provided | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 241 of the MYO7A protein (p.Arg241His). This variant is present in population databases (rs111033284, gnomAD 0.006%). This missense change has been observed in individuals with Usher syndrome or autosomal recessive non-syndromic sensorineural deafness (PMID: 21436283, 23770805, 26226137, 31479088). ClinVar contains an entry for this variant (Variation ID: 43340). 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 |
RCV001852752 | SCV002552767 | likely pathogenic | not provided | 2022-03-16 | criteria provided, single submitter | clinical testing | Identified with a second MYO7A variant in siblings with retinitis pigmentosa in published literature; information regarding hearing status was not available (Khateb et al., 2020); 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: 10930322, 23770805, 26309859, 26338283, 16963483, 26226137, 30303587, 21436283, 31479088) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323371 | SCV004030133 | pathogenic | Usher syndrome | 2023-07-28 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.722G>A (p.Arg241His) 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 1.6e-05 in 248492 control chromosomes (gnomAD). c.722G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Usher Syndrome or autosomal recessive non-syndromic sensorineural deafness (examples: Roux_2011, Shahzad_2013, Bademci2016). 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: 23770805 , 26226137 , 21436283). Other variants affecting the same residue (p.Arg241Cys, p.Arg241Gly) have been classified pathogenic in ClinVar suggesting this residue may be critical for normal function of the protein (CV IDs 438180, 2137200). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Laboratory for Molecular Medicine, |
RCV000036247 | SCV000059899 | likely pathogenic | Rare genetic deafness | 2007-08-22 | no assertion criteria provided | clinical testing | |
| University of Washington Center for Mendelian Genomics, |
RCV001291466 | SCV001479970 | likely pathogenic | Hearing loss, autosomal recessive | no assertion criteria provided | research |