Submissions for variant NM_000071.3(CBS):c.573G>A (p.Thr191=)

gnomAD frequency: 0.00615  dbSNP: rs73906420

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000179709	SCV000167561	benign	not specified	2013-03-06	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.
Eurofins Ntd Llc (ga)	RCV000179709	SCV000232000	benign	not specified	2015-02-19	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000179709	SCV000268835	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	Thr191Thr in exon 7 of CBS: This variant is not expected to have clinical signif icance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.7% (64/8600) of Euro pean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs73906420).
Labcorp Genetics (formerly Invitae), Labcorp	RCV002228267	SCV000283387	benign	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310681	SCV000317357	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2014-07-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001795225	SCV000602916	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000755228	SCV001298057	benign	Classic homocystinuria	2017-06-26	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 rule this variant out of causing disease. Therefore, this variant is classified as benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000179709	SCV001338212	benign	not specified	2020-02-24	criteria provided, single submitter	clinical testing	Variant summary: CBS c.573G>A alters a non-conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0059 in 248930 control chromosomes in the gnomAD database, including 12 homozygotes. The observed variant frequency is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in CBS causing Homocystinuria phenotype (0.003), strongly suggesting that the variant is benign. Four ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001795225	SCV002544674	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	CBS: BP4, BP7, BS1, BS2
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277186	SCV002566505	benign	Connective tissue disorder	2021-12-06	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001795225	SCV005206367	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000179709	SCV001809040	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000179709	SCV001917201	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001795225	SCV002036688	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000755228	SCV002083803	benign	Classic homocystinuria	2019-12-03	no assertion criteria provided	clinical testing