ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4010G>A (p.Arg1337Gln)

gnomAD frequency: 0.00005  dbSNP: rs368575559
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158627 SCV000208562 uncertain significance not provided 2021-11-09 criteria provided, single submitter clinical testing Reported in one patient with HCM and one patient with left ventricular hypertrabeculation (Berge et al., 2014; Miszalski-Jamka et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#181238; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 24111713, 25649125, 22958901, 28798025, 26582918)
Ambry Genetics RCV000619617 SCV000740099 likely benign Cardiovascular phenotype 2022-10-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV000778008 SCV000914117 uncertain significance Cardiomyopathy 2023-04-28 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 1337 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 performed for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 24111713) and in an individual affected with left ventricular hypertrabeculation (PMID: 28798025). This variant has been identified in 34/281574 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The elevated variant allele frequency in the general population indicates that this variant may not be disease-causing. However, additional studies are necessary to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001225105 SCV001397341 uncertain significance Hypertrophic cardiomyopathy 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1337 of the MYH7 protein (p.Arg1337Gln). This variant is present in population databases (rs368575559, gnomAD 0.06%). This missense change has been observed in individual(s) with left ventricular noncompaction or hypertrophic cardiomyopathy (PMID: 24111713, 28798025). ClinVar contains an entry for this variant (Variation ID: 181238). 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. 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 RCV002492624 SCV002791520 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 2021-12-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000158627 SCV003917316 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing MYH7: PP2, PP3
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000158627 SCV001798041 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000158627 SCV001923752 uncertain significance not provided no assertion criteria provided clinical testing

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