Submissions for variant NM_000071.3(CBS):c.699C>T (p.Tyr233=)

gnomAD frequency: 0.28613  dbSNP: rs234706

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078110	SCV000109948	benign	not specified	2014-03-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000078110	SCV000167563	benign	not specified	2013-08-13	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000078110	SCV000268836	benign	not specified	2014-12-02	criteria provided, single submitter	clinical testing	p.Tyr233Tyr in exon 8 of CBS: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 34% (2960/8600) of E uropean American chromosomes and 23% (1021/4406) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs234706).
PreventionGenetics, part of Exact Sciences	RCV000078110	SCV000301905	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310652	SCV000317682	benign	Familial thoracic aortic aneurysm and aortic dissection	2014-11-24	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000600783	SCV000436221	benign	Classic homocystinuria	2018-03-06	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811356	SCV000885144	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Invitae	RCV002228202	SCV001729928	benign	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000600783	SCV001775581	benign	Classic homocystinuria	2021-07-14	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277141	SCV002566527	benign	Connective tissue disorder	2022-07-18	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000600783	SCV000734090	benign	Classic homocystinuria		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000600783	SCV000745585	benign	Classic homocystinuria	2016-12-05	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000600783	SCV001462123	benign	Classic homocystinuria	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000078110	SCV001924667	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078110	SCV001955543	benign	not specified		no assertion criteria provided	clinical testing