ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4438A>G (p.Ser1480Gly)

gnomAD frequency: 0.00002  dbSNP: rs930701630
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000647061 SCV000768848 uncertain significance Hypertrophic cardiomyopathy 14 2024-09-06 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1480 of the MYH6 protein (p.Ser1480Gly). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 537959). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002331213 SCV002633171 uncertain significance Cardiovascular phenotype 2023-11-07 criteria provided, single submitter clinical testing The p.S1480G variant (also known as c.4438A>G), located in coding exon 29 of the MYH6 gene, results from an A to G substitution at nucleotide position 4438. The serine at codon 1480 is replaced by glycine, an amino acid with similar properties. This variant was detected in a cardiomyopathy genetic testing cohort; however, clinical details were limited (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002493028 SCV002813477 uncertain significance Hypertrophic cardiomyopathy 1; Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-11-02 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224366 SCV003920241 uncertain significance Dilated cardiomyopathy 1EE; Hypertrophic cardiomyopathy 14; Atrial septal defect 3; Sick sinus syndrome 3, susceptibility to 2021-03-30 criteria provided, single submitter clinical testing MYH6 NM_002471.3 exon 31 p.Ser1480Gly (c.4438A>G):This variant has not been reported in the literature but is present in 0.002% (1/34580) of Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/14-23857054-T-C). This variant is present in ClinVar (Variation ID:537939). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, computational tools designed to predict splicing suggest a potential effect from this variant. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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