ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.457del (p.His153fs) (rs397516224)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035922 SCV000059573 likely pathogenic Primary dilated cardiomyopathy 2016-04-06 criteria provided, single submitter clinical testing The p.His153ThrfsX14 variant in MYH7 has been identified in one individual with cardiomyopathy (in trans with another MYH7 variant) but has not been observed in large population studies. This variant is predicted to cause a frameshift, whic h alters the protein?s amino acid sequence beginning at position 153 and leads t o a premature termination codon 14 amino acids downstream. This alteration is th en predicted to lead to a truncated or absent protein. Although heterozygous los s-of-function (LOF) variants in MYH7, such as this variant, are not believed to be pathogenic for the dominant condition more classically associated to MYH7, wh en a LOF variant is found in trans with another variant affecting function, a mo re severe and early-onset cardiomyopathy presentation can occur (LMM unpublished data). It should be noted that loss of function variants in the MYH7 gene are very rare and therefore an understanding of their potential impact is not well s tudied. In summary, this variant leads to a predicted loss-of-function of the pr otein and, although additional studies are required to fully establish its clini cal significance, it is likely pathogenic for a recessive presentation.
Invitae RCV000820956 SCV000961695 uncertain significance Hypertrophic cardiomyopathy 2018-07-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His153Thrfs*14) in the MYH7 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 20474083). ClinVar contains an entry for this variant (Variation ID: 43028). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH7 cause disease. 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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