ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4816C>T (p.Arg1606Cys) (rs200530211)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172042 SCV000051002 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154606 SCV000204279 uncertain significance not specified 2016-09-12 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000172042 SCV000208606 uncertain significance not provided 2018-02-21 criteria provided, single submitter clinical testing The R1606C variant of uncertain significance in the MYH7 gene has been previously reported in association with HCM (Helms et al., 2014; Helms et al., 2016; Homburger et al., 2016; Walsh et al., 2017). This variant has also been identified in several individuals referred for cardiomyopathy genetic testing at GeneDx; however, one of these probands harbors an additional cardiogenetic variant that likely contributes to the phenotype, and segregation analysis has been uninformative thus far. In addition, R1606C has been reported in an individual from a cohort of patients undergoing whole exome sequencing that were not selected for cardiomyopathy, arrhythmia or a family history of sudden death (Ng et al., 2013). Nevertheless, R1606C is not observed at a significant frequency in additional large population cohorts (Lek et al., 2016). The R1606C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.
Invitae RCV000470391 SCV000546188 uncertain significance Hypertrophic cardiomyopathy 2019-09-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1606 of the MYH7 protein (p.Arg1606Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with hypertrophic cardiomyopathy (PMID: 25031304, 27247418, 27532257). ClinVar contains an entry for this variant (Variation ID: 177945). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Illumina Clinical Services Laboratory,Illumina RCV001112385 SCV001270041 uncertain significance Familial hypertrophic cardiomyopathy 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001112386 SCV001270042 uncertain significance Dilated cardiomyopathy 1S 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001112387 SCV001270043 uncertain significance Myosin storage myopathy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001112388 SCV001270044 uncertain significance Myopathy, distal, 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color RCV001184477 SCV001350450 uncertain significance Cardiomyopathy 2019-06-29 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.