Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003492291 | SCV004240803 | pathogenic | Usher syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.731G>C (p.Arg244Pro) results in a non-conservative amino acid change located in the Myosin head, motor domain (IPR001609) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 247714 control chromosomes. c.731G>C has been reported in the literature in multiple individuals affected with Usher Syndrome (example, Liu_1997). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect in mouse MYO7A resulted in disabled motor function of MYO7A based on ATPase activity assay and in vitro localization assay in cultured mouse inner ear hair cells (Riazuddin_2008). The following publications have been ascertained in the context of this evaluation (PMID: 9718356, 18181211). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000012627 | SCV000032862 | pathogenic | Autosomal recessive nonsyndromic hearing loss 2 | 2008-04-01 | no assertion criteria provided | literature only |