Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000156361 | SCV000206079 | likely pathogenic | Rare genetic deafness | 2017-07-17 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
| Institute of Medical Genetics and Applied Genomics, |
RCV002463651 | SCV002758017 | likely pathogenic | Usher syndrome type 1 | 2022-12-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003398813 | SCV004121959 | likely pathogenic | Usher syndrome | 2023-10-03 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.1A>G (p.Met1Val) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. The next downstream in-frame initiation codon is at Met12. Another disruption of the initiator codon has been determined to be pathogenic in ClinVar (c.3G>A, p.Met1Ile). Three of three in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 247312 control chromosomes. c.1A>G has been reported in the literature (Hanany_2020). This report does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31964843). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV003764969 | SCV004635644 | pathogenic | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the MYO7A mRNA. The next in-frame methionine is located at codon 12. This variant is present in population databases (rs797044518, gnomAD 0.004%). Disruption of the initiator codon has been observed in individuals with clinical features of autosome recessive MYO7A-related conditions (PMID: 30459346; Invitae). ClinVar contains an entry for this variant (Variation ID: 179567). This variant disrupts a region of the MYO7A protein in which other variant(s) (p.Gly7Val ) have been determined to be pathogenic (PMID: 30303587). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |