Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000036123 | SCV000059775 | pathogenic | Rare genetic deafness | 2010-08-13 | criteria provided, single submitter | clinical testing | The Pro1244fs variant in MYO7A has not been reported in the literature nor previ ously identified by our laboratory. However, this variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at codon 1244 and leads to a premature stop codon 64 codons downstream. This alteration i s then predicted to lead to a truncated or absent protein. In summary, this vari ant meets our criteria to be classified as pathogenic. |
| Invitae | RCV001388466 | SCV001589465 | pathogenic | not provided | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Pro1244Alafs*64) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 43219). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155050 | SCV003845002 | likely pathogenic | Usher syndrome | 2023-02-20 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.3728dupC (p.Pro1244AlafsX64) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been reported in HGMD in association with Retinitis pigmentosa, Deafness, non-syndromic, autosomal recessive and Usher syndrome. The variant was absent in 183422 control chromosomes. To our knowledge, no occurrence of c.3728dupC in individuals affected with Usher Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |