ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.610C>T (p.Arg204Cys) (rs397516259)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158748 SCV000208683 pathogenic not provided 2013-06-07 criteria provided, single submitter clinical testing p.Arg204Cys (CGC>TGC): c.610 C>T in exon 7 of the MYH7 gene (NM_000257.2). The Arg204Cys mutation in the MYH7 gene has not been published as a disease-causing mutation or as a benign polymorphism to our knowledge, however it has been observed in other unrelated individuals tested for HCM at GeneDx. Furthermore, Arg204Cys was not observed in the 1000 Genomes database or in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Arg204Cys results in a non-conservative amino acid substitution at a position that is well conserved across species. Mutations affecting this same residue (Arg204His) and nearby residues (Ala199Val, Ile201Thr, Lys207Gln) have been reported in association with cardiomyopathy, further supporting the functional importance of this residue and this region of the protein. In summary, Arg204Cys in the MYH7 gene is interpreted as a disease-causing mutation. The variant is found in HCM panel(s).
Invitae RCV000628868 SCV000749776 uncertain significance Hypertrophic cardiomyopathy 2019-07-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 204 of the MYH7 protein (p.Arg204Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs397516259, ExAC 0.02%). This variant has been reported in individuals affected with hypertrophic cardiomyopathy (PMID: 27247418, 27532257). ClinVar contains an entry for this variant (Variation ID: 181315). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg204His) has been determined to be pathogenic (PMID: 12707239, 27247418, 24111713, 27841901, 23816408, 24865491, 27532257). This suggests that the arginine residue is critical for MYH7 protein function and that other missense substitutions at this position may also be pathogenic. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000158748 SCV001149193 uncertain significance not provided 2017-03-01 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.