Submissions for variant NM_000435.3(NOTCH3):c.6619C>T (p.Arg2207Trp)

gnomAD frequency: 0.00006  dbSNP: rs753170185

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000996808	SCV001151737	uncertain significance	not provided	2019-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001123437	SCV001282278	uncertain significance	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000996808	SCV002151854	likely benign	not provided	2022-08-16	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002481780	SCV002790990	uncertain significance	Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1; Lateral meningocele syndrome; Myofibromatosis, infantile, 2	2022-03-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003243392	SCV003942643	uncertain significance	Inborn genetic diseases	2023-03-21	criteria provided, single submitter	clinical testing	The c.6619C>T (p.R2207W) alteration is located in exon 33 (coding exon 33) of the NOTCH3 gene. This alteration results from a C to T substitution at nucleotide position 6619, causing the arginine (R) at amino acid position 2207 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003898016	SCV004717616	likely benign	NOTCH3-related condition	2022-10-12	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).