ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.541G>A (p.Gly181Arg) (rs760187215)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations RCV000757956 SCV000882824 likely pathogenic Primary dilated cardiomyopathy; Left ventricular noncompaction cardiomyopathy 2018-12-06 criteria provided, single submitter research The c.541G>A (p.G181R) variant was previously reported in HGMD database (CM1616486) as a DM(disease causing mutation) and in Atlas of Cardiac Genetic Variations. This is a rare variant with low frequency in population databases. Computational evidence supports a deleterious effect. Also c.541G>A (p.G181R) is located in a domain without benign variation (Walsh et al., 2017). We consider this evidence enough to classify c.541G>A (p.G181R) as likely pathogenic.
Invitae RCV001207953 SCV001379321 uncertain significance Hypertrophic cardiomyopathy 2019-08-16 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 181 of the MYH7 protein (p.Gly181Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs760187215, ExAC 0.006%). This variant has been observed in an individual affected with MYH7-related conditions (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 619082). 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 C15"). 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.

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