ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.218T>C (p.Leu73Pro)

gnomAD frequency: 0.00003  dbSNP: rs372188355
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672457 SCV000797563 uncertain significance Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2018-01-31 criteria provided, single submitter clinical testing
Invitae RCV001347349 SCV001541605 uncertain significance not provided 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 73 of the MYO7A protein (p.Leu73Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with autosomal recessive non-syndromic hearing loss (PMID: 26969326). ClinVar contains an entry for this variant (Variation ID: 556446). 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. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003387907 SCV004100131 uncertain significance not specified 2023-09-26 criteria provided, single submitter clinical testing Variant summary: MYO7A c.218T>C (p.Leu73Pro) results in a non-conservative amino acid change located in the Myosin head, motor domain (IPR001609) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-06 in 221926 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.218T>C has been reported in the literature in at least one compound heterozygous individual affected with autosomal recessive non-syndromic hearing loss (e.g., Sloan-Heggen_2016). 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: 26969326). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014; all submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001829877 SCV002093104 uncertain significance Usher syndrome type 1B 2020-07-20 no assertion criteria provided clinical testing

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