ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5013C>G (p.Ile1671Met)

gnomAD frequency: 0.00002  dbSNP: rs779978846
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001338746 SCV001532439 uncertain significance Hypertrophic cardiomyopathy 2024-08-10 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1671 of the MYH7 protein (p.Ile1671Met). This variant is present in population databases (rs779978846, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of MYH7-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1035824). 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 MYH7 protein function with a negative predictive value of 95%. 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 RCV002350615 SCV002645482 uncertain significance Cardiovascular phenotype 2024-12-26 criteria provided, single submitter clinical testing The p.I1671M variant (also known as c.5013C>G), located in coding exon 33 of the MYH7 gene, results from a C to G substitution at nucleotide position 5013. The isoleucine at codon 1671 is replaced by methionine, an amino acid with highly similar properties. This variant was reported in individual(s) with features consistent with hypertrophic cardiomyopathy (HCM) (Kurzlechner LM et al. J Pers Med, 2022 Apr;12:[ePub ahead of print]; Ambry internal data). 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. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV004005153 SCV004830270 uncertain significance Cardiomyopathy 2023-06-28 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 1671 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 3/251406 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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