ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3613G>A (p.Glu1205Lys) (rs727505026)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156452 SCV000206171 uncertain significance not specified 2014-04-04 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Glu1205Lys variant in MYH7 has been reported in 1 individual with HCM (Waldmuller 2008) and was absent large population studies (NHLBI Exome Sequencing Project (http://evs .gs.washington.edu/EVS/). This variant was predicted to be pathogenic using a co mputational tool clinically validated by our laboratory. This tool's pathogenic prediction is estimated to be correct 94% of the time (Jordan 2011). Although th is data supports that the Glu1205Lys variant may be pathogenic, additional studi es are needed to fully assess its clinical significance.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000414966 SCV000492919 likely pathogenic Hypertrophic cardiomyopathy; Dyspnea 2014-11-28 criteria provided, single submitter clinical testing
Invitae RCV000534779 SCV000623702 uncertain significance Hypertrophic cardiomyopathy 2017-08-23 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1205 of the MYH7 protein (p.Glu1205Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 18258667, 26914223, 24111713). ClinVar contains an entry for this variant (Variation ID: 179656). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). 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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