ClinVar Miner

Submissions for variant NM_002473.6(MYH9):c.4297C>T (p.Arg1433Cys)

gnomAD frequency: 0.00005  dbSNP: rs727503286
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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 RCV000151332 SCV000199302 uncertain significance not specified 2014-07-29 criteria provided, single submitter clinical testing The Arg1433Cys variant in MYH9 has not been previously reported in individuals w ith hearing loss or in large population studies. Computational prediction tools and conservation analyses suggest that the Arg1433Cys variant may impact the pro tein, though this information is not predictive enough to determine pathogenicit y. In summary, the clinical significance of the Arg1433Cys variant is uncertain.
Illumina Laboratory Services, Illumina RCV000276612 SCV000438360 benign MYH9-related disorder 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV000331644 SCV000438361 uncertain significance Autosomal dominant nonsyndromic hearing loss 17 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001850062 SCV002221213 uncertain significance not provided 2023-09-17 criteria provided, single submitter clinical testing 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. 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 MYH9 protein function. ClinVar contains an entry for this variant (Variation ID: 164438). This missense change has been observed in individual(s) with autosomal dominant deafness (PMID: 33710140). This variant is present in population databases (rs727503286, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1433 of the MYH9 protein (p.Arg1433Cys).

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