ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.5507T>C (p.Leu1836Pro)

gnomAD frequency: 0.00001  dbSNP: rs1164918878
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668455 SCV000793062 uncertain significance Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-07-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003558497 SCV004294149 likely pathogenic not provided 2023-04-03 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 553080). This missense change has been observed in individual(s) with autosomal recessive Usher syndrome (PMID: 27460420). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1836 of the MYO7A protein (p.Leu1836Pro).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005056409 SCV005726228 uncertain significance not specified 2024-11-15 criteria provided, single submitter clinical testing Variant summary: MYO7A c.5507T>C (p.Leu1836Pro) results in a non-conservative amino acid change located in the MyTH4 domain profile (IPR000857) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.5507T>C has been reported in the literature in an individual affected with Usher Syndrome (Jaijo_2007, Maltese_2022). These report(s) do 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 publications have been ascertained in the context of this evaluation (PMID: 17361009, 35836572). ClinVar contains an entry for this variant (Variation ID: 553080). Based on the evidence outlined above, the variant was classified as uncertain significance.

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