Submissions for variant NM_000435.3(NOTCH3):c.509A>G (p.His170Arg)

gnomAD frequency: 0.00184  dbSNP: rs147373451

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000263508	SCV000411015	likely benign	Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455302	SCV000539943	likely benign	not specified	2016-04-25	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 5 individuals with CADASIL. Also identified in 3 individuals with ischemic strokes, but the frequency was not different in controls. No segregation data available. No new publications since 2013. MAF 0.4%, too high to be consistent for a pathogenic role in AD highly penetrant disease.
Athena Diagnostics Inc	RCV000263508	SCV000677224	benign	Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1	2017-05-31	criteria provided, single submitter	clinical testing
Invitae	RCV000865482	SCV001006459	benign	not provided	2024-01-26	criteria provided, single submitter	clinical testing
Mendelics	RCV000263508	SCV001141028	likely benign	Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000865482	SCV001471359	likely benign	not provided	2023-10-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002495036	SCV002795849	likely benign	Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1; Lateral meningocele syndrome; Myofibromatosis, infantile, 2	2022-05-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000865482	SCV004011037	benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	NOTCH3: PP2, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003922398	SCV004741709	likely benign	NOTCH3-related condition	2019-03-04	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).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000865482	SCV001808854	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000865482	SCV001932793	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000865482	SCV002035873	likely benign	not provided		no assertion criteria provided	clinical testing