Submissions for variant NM_000432.4(MYL2):c.325G>T (p.Glu109Ter)

dbSNP: rs2136770789

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001944563	SCV002127986	uncertain significance	Hypertrophic cardiomyopathy 10	2021-07-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu109*) in the MYL2 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 MYL2 cause disease. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MYL2-related conditions. 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.
All of Us Research Program, National Institutes of Health	RCV004808141	SCV005431212	uncertain significance	Hypertrophic cardiomyopathy	2024-03-24	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 5 of the MYL2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with MYL2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Clinical relevance of loss-of-function MYL2 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.