ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2137A>G (p.Ile713Val)

gnomAD frequency: 0.00001  dbSNP: rs1339799654
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001055617 SCV001220017 uncertain significance Hypertrophic cardiomyopathy 2023-07-22 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 MYH7 protein function. ClinVar contains an entry for this variant (Variation ID: 851259). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 713 of the MYH7 protein (p.Ile713Val).
Ambry Genetics RCV002429667 SCV002730037 uncertain significance Cardiovascular phenotype 2023-05-12 criteria provided, single submitter clinical testing The p.I713V variant (also known as c.2137A>G), located in coding exon 17 of the MYH7 gene, results from an A to G substitution at nucleotide position 2137. The isoleucine at codon 713 is replaced by valine, an amino acid with highly similar properties. This alteration is located in the myosin head domain, which contains a statistically significant clustering of pathogenic missense variants (Homburger JR et al. Proc Natl Acad Sci U S A, 2016 06;113:6701-6; Walsh R et al. Genet Med, 2017 02;19:192-203; Ambry internal data). 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 RCV002505609 SCV002816399 uncertain significance Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy 2021-10-12 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV003532363 SCV004356928 uncertain significance Cardiomyopathy 2023-04-26 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 713 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 cardiovascular disorders in the literature. This variant has been identified in 1/251460 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.
All of Us Research Program, National Institutes of Health RCV003532363 SCV004822514 uncertain significance Cardiomyopathy 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 713 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 cardiovascular disorders in the literature. This variant has been identified in 1/251460 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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