Submissions for variant NM_000435.3(NOTCH3):c.1931T>A (p.Val644Asp)

gnomAD frequency: 0.00063  dbSNP: rs148046938

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000865115	SCV001006031	likely benign	not provided	2023-12-21	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001288881	SCV001476278	benign	not specified	2019-09-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000865115	SCV002038986	uncertain significance	not provided	2021-06-18	criteria provided, single submitter	clinical testing	Reported previously, with alternate nomenclature c.2009T>A, as a variant of uncertain pathogenic significance in three individuals with leukoencephalopathy; detailed clinical and segregation information was not provided (Ungaro C et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32573853, 19006080)
CeGaT Center for Human Genetics Tuebingen	RCV000865115	SCV002563510	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	NOTCH3: BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000865115	SCV004564737	likely benign	not provided	2023-10-23	criteria provided, single submitter	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000865115	SCV001799881	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000865115	SCV001808519	uncertain significance	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000865115	SCV001963586	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000865115	SCV001964309	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004538229	SCV004748839	likely benign	NOTCH3-related disorder	2022-01-27	no assertion criteria provided	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).