ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.4708A>G (p.Ile1570Val)

dbSNP: rs1258827113
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001219855 SCV001391814 uncertain significance Hypertrophic cardiomyopathy 14 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1570 of the MYH6 protein (p.Ile1570Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32746448). ClinVar contains an entry for this variant (Variation ID: 948570). 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 not expected to disrupt MYH6 protein function with a negative predictive value of 80%. 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 RCV003380896 SCV004088733 uncertain significance Cardiovascular phenotype 2023-07-11 criteria provided, single submitter clinical testing The p.I1570V variant (also known as c.4708A>G), located in coding exon 31 of the MYH6 gene, results from an A to G substitution at nucleotide position 4708. The isoleucine at codon 1570 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in a pediatric cardiomyopathy cohort (Burstein DS et al. Pediatr Res, 2021 May;89:1470-1476). This amino acid position is not well 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.

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