Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000036120 | SCV000059772 | uncertain significance | not specified | 2008-03-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001852744 | SCV002136461 | uncertain significance | not provided | 2022-12-25 | criteria provided, single submitter | clinical testing | Studies have shown that this missense change alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 23451239). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt MYO7A protein function. ClinVar contains an entry for this variant (Variation ID: 43216). This missense change has been observed in individual(s) with clinical features of Usher syndrome (PMID: 17361009). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1218 of the MYO7A protein (p.Gly1218Arg). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230377 | SCV003928883 | pathogenic | Usher syndrome | 2023-04-27 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.3652G>A (p.Gly1218Arg) results in a non-conservative amino acid change located in the MyTH4 domain (IPR000857) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a cryptic exonic 3 acceptor site. Experimental evidence indicate the variant affects mRNA splicing (Aparisi_2013). The variant allele was found at a frequency of 5.8e-06 in 172088 control chromosomes (gnomAD). c.3652G>A has been reported in the literature in individuals affected with Usher Syndrome (Jaijo_2007, Baux_2017, Mansard_2021). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 23451239, 29196752, 17361009, 34948090, 33258288). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as pathogenic. |