Submissions for variant NM_000257.4(MYH7):c.5556C>G (p.Tyr1852Ter)

dbSNP: rs730880823

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158708	SCV000208643	uncertain significance	not provided	2020-10-20	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease; This variant is associated with the following publications: (PMID: 29892087, 31983221)
Invitae	RCV000821040	SCV000961780	uncertain significance	Hypertrophic cardiomyopathy	2024-01-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr1852*) in the MYH7 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH7 cause disease. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with dilated cardiomyopathy (PMID: 29892087). ClinVar contains an entry for this variant (Variation ID: 181287). 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.
Revvity Omics, Revvity	RCV000158708	SCV003817747	uncertain significance	not provided	2020-10-08	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003531999	SCV004359502	uncertain significance	Cardiomyopathy	2022-12-13	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 37 of the MYH7 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 29892087). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Clinical relevance of loss-of-function MYH7 truncation variants in autosomal dominant cardiovascular disorders is not clearly established. The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.