Submissions for variant NM_000257.4(MYH7):c.732+2T>G

dbSNP: rs1555338658

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000533348	SCV000623756	pathogenic	Hypertrophic cardiomyopathy	2022-04-01	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 454395). Disruption of this splice site has been observed in individual(s) with clinical features of left ventricular noncompaction (PMID: 18506004; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 8 of the MYH7 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH7 cause disease. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000678820	SCV000805006	likely pathogenic	Left ventricular noncompaction	2015-05-05	no assertion criteria provided	clinical testing