Submissions for variant NM_000435.3(NOTCH3):c.2580C>T (p.Asn860=)

gnomAD frequency: 0.00035  dbSNP: rs201436750

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000365121	SCV000410991	benign	Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1	2018-01-12	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae	RCV000872118	SCV001013888	benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000872118	SCV001143372	benign	not provided	2019-06-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000872118	SCV004140312	benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	NOTCH3: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003969934	SCV004781724	likely benign	NOTCH3-related condition	2019-03-20	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).