Submissions for variant NM_000435.3(NOTCH3):c.831G>A (p.Glu277=)

gnomAD frequency: 0.00021  dbSNP: rs145049433

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000876481	SCV001019058	likely benign	not provided	2023-10-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000876481	SCV001151745	likely benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	NOTCH3: BP4, BP7
Illumina Laboratory Services, Illumina	RCV001124921	SCV001283928	likely benign	Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
PreventionGenetics, part of Exact Sciences	RCV003955742	SCV004776196	likely benign	NOTCH3-related condition	2020-02-20	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).