Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001884236 | SCV002153491 | uncertain significance | not provided | 2024-04-25 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1841 of the MYO7A protein (p.Thr1841Met). This variant is present in population databases (rs746667217, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of MYO7A-related conditions (PMID: 34837038). ClinVar contains an entry for this variant (Variation ID: 1387794). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Fulgent Genetics, |
RCV002482689 | SCV002790626 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 | 2021-08-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003230709 | SCV003928885 | uncertain significance | not specified | 2023-04-27 | criteria provided, single submitter | clinical testing | Variant summary: MYO7A c.5522C>T (p.Thr1841Met) results in a non-conservative amino acid change located in the MyTH4 domain (IPR000857) 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 6.4e-05 in 220012 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MYO7A causing Usher Syndrome (6.4e-05 vs 0.0061), allowing no conclusion about variant significance. c.5522C>T has been reported in the literature in an individual affected with bilateral hearing loss (Adeyemo_2022) without strong evidence for causality. 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 publications have been ascertained in the context of this evaluation (PMID: 34837038). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |