ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1097T>C (p.Leu366Pro)

gnomAD frequency: 0.00001  dbSNP: rs397516281
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036037 SCV000059689 likely pathogenic Rare genetic deafness 2012-07-26 criteria provided, single submitter clinical testing The Leu366Pro variant in MYO7A has been reported in trans with likely pathogenic MYO7A variants in two probands with Usher syndrome type I (Jaijo 2007; LMM unpu blished data). In addition, it was absent from >8,000 European American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS/). In summary, this variant is likely pathogenic, though add itional studies are required to fully establish its clinical significance.
Counsyl RCV000666645 SCV000790973 likely pathogenic Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-04-18 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268216 SCV001446974 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001268216 SCV001576697 pathogenic not provided 2023-11-09 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 366 of the MYO7A protein (p.Leu366Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Usher syndrome (PMID: 17361009, 27460420). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 43133). 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.

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