Submissions for variant NM_002474.3(MYH11):c.2344C>T (p.Arg782Ter)

dbSNP: rs777173010

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001525708	SCV001735888	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2021-08-31	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 20 of the MYH11 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 cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The role of loss-of-function MYH11 truncation and splice 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568104	SCV002963013	pathogenic	Aortic aneurysm, familial thoracic 4	2022-05-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg789*) in the MYH11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYH11 are known to be pathogenic (PMID: 25407000, 29575632). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1172097). This variant has not been reported in the literature in individuals affected with MYH11-related conditions.