ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.67C>T (p.Arg23Trp)

gnomAD frequency: 0.00005  dbSNP: rs730880828
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158722 SCV000208657 uncertain significance not provided 2015-08-19 criteria provided, single submitter clinical testing p.Arg23Trp (CGG>TGG): c.67 C>T in exon 3 of the MYH7 gene (NM_000257.2). The Arg23Trp variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg23Trp results in a non-conservative amino acid substitution of a positively charged Arginine with a non-polar Tryptophan at a position that is conserved across species. In silico analysis predicts Arg23Trp is probably damaging to the protein structure/function. The NHLBI ESP Exome Variant Server reports Arg23Trp was not observed in approximately 6,500 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Nevertheless, no definitive mutations in nearby residues have been reported in association with HCM. With the clinical and molecular information available at this time, we cannot definitively determine if Arg23Trp is a disease-causing mutation or a rare benign variant. The variant is found in HCM panel(s).
Color Diagnostics, LLC DBA Color Health RCV000778010 SCV000914119 uncertain significance Cardiomyopathy 2023-07-25 criteria provided, single submitter clinical testing This missense variant replaces arginine with tryptophan at codon 23 of the MYH7 protein. Computational prediction suggests that this variant may have a deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 30847666), in an individual affected with left ventricular noncompaction (PMID: 28855170, 32183154, 32600061), and in an individual affected with noncompaction cardiomyopathy (PMID: 30847666). This variant has been identified in 7/282814 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.
Invitae RCV001235446 SCV001408132 uncertain significance Hypertrophic cardiomyopathy 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 23 of the MYH7 protein (p.Arg23Trp). This variant is present in population databases (rs730880828, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of MYH7-related conditions (PMID: 28855170, 30847666). ClinVar contains an entry for this variant (Variation ID: 181295). 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 expected to disrupt MYH7 protein function with a positive 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.
Fulgent Genetics, Fulgent Genetics RCV002505190 SCV002814401 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 2021-07-28 criteria provided, single submitter clinical testing
Revvity Omics, Revvity Omics RCV000158722 SCV003817765 uncertain significance not provided 2022-06-07 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV000158722 SCV001919239 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000158722 SCV001953875 uncertain significance not provided no assertion criteria provided clinical testing

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