ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.602T>C (p.Ile201Thr) (rs397516258)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000035988 SCV000059640 likely pathogenic Primary dilated cardiomyopathy 2014-01-02 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000158747 SCV000208682 likely pathogenic not provided 2020-02-28 criteria provided, single submitter clinical testing Reported in ClinVar as a likely pathogenic variant (ClinVar Variant ID 43093; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 16416045, 22337857, 25714468, 27802374, 21424860, 18555187, 24474197, 15769782, 28606303, 24503780, 29666183, 27532257, 31317183, 32013205, 31737537, 30847666)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587084 SCV000696359 likely pathogenic Cardiovascular phenotype 2016-06-20 criteria provided, single submitter clinical testing
Invitae RCV001054799 SCV001219150 pathogenic Hypertrophic cardiomyopathy 2020-10-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 201 of the MYH7 protein (p.Ile201Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with dilated cardiomyopathy in a family (PMID: 15769782), and has been reported in unrelated individuals affected with this condition (PMID: 27532257, Invitae). ClinVar contains an entry for this variant (Variation ID: 43093). 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: Benign; Align-GVGD: Class C0). 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). For these reasons, this variant has been classified as Pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170747 SCV001333352 likely pathogenic Cardiomyopathy 2018-03-28 criteria provided, single submitter clinical testing
Clinical Genetics,Academic Medical Center RCV000158747 SCV001920032 likely pathogenic not provided no assertion criteria provided clinical testing

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