ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5342G>A (p.Arg1781His) (rs397516246)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000234735 SCV000492983 uncertain significance Hypertrophic cardiomyopathy 2014-01-21 criteria provided, single submitter clinical testing
Invitae RCV000234735 SCV000284285 likely pathogenic Hypertrophic cardiomyopathy 2017-06-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1781 of the MYH7 protein (p.Arg1781His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs397516246, ExAC 0.006%). This variant has been reported in several unrelated individuals with hypertrophic cardiomyopathy (PMID: 17125710, 27532257, Invitae). ClinVar contains an entry for this variant (Variation ID: 43064). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035959 SCV000059611 uncertain significance not specified 2017-08-29 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg1781Hi s variant in MYH7 has been reported in 3 individuals with HCM (Laredo 2006, LMM data). It has been identified in 1/16512 South Asian chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs397516246). Arginine (Arg) at position 1781 is highly conserved across evolutionarily distan t species and the change to histidine (His) was predicted to be pathogenic using a computational tool clinically validated by our laboratory. This tool's pathog enic prediction is estimated to be correct 94% of the time (Jordan 2011). In sum mary, while there is some suspicion for a pathogenic role, the clinical signific ance of the p.Arg1781His variant is uncertain.

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