Submissions for variant NM_031443.4(CCM2):c.1078A>T (p.Lys360Ter)

dbSNP: rs767248510

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001053267	SCV001217523	pathogenic	Cerebral cavernous malformation 2	2019-12-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the CCM2 protein. Other variant(s) that disrupt this region (p.Glu417Glyfs*3) have been determined to be pathogenic (PMID: 14740320). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with CCM2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the CCM2 gene (p.Lys360*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 85 amino acids of the CCM2 protein.
PreventionGenetics, part of Exact Sciences	RCV003396677	SCV004106075	likely pathogenic	CCM2-related disorder	2023-08-25	criteria provided, single submitter	clinical testing	The CCM2 c.1078A>T variant is predicted to result in premature protein termination (p.Lys360*). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in CCM2 are expected to be pathogenic. This variant is interpreted as pathogenic.