Submissions for variant NM_000071.3(CBS):c.1080C>T (p.Ala360=)

gnomAD frequency: 0.30942  dbSNP: rs1801181

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078107	SCV000109945	benign	not specified	2014-03-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001356690	SCV000167569	benign	not provided	2018-10-04	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000078107	SCV000268832	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	Ala360Ala in exon 12 of CBS: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 35.9% (3087/8594) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1801181).
PreventionGenetics, part of Exact Sciences	RCV000078107	SCV000301903	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002310651	SCV000317681	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: 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.
Illumina Laboratory Services, Illumina	RCV000611179	SCV000436211	benign	Classic homocystinuria	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 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	RCV001356690	SCV000602915	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000611179	SCV000743128	benign	Classic homocystinuria	2017-07-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002228200	SCV001729927	benign	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000611179	SCV001776149	benign	Classic homocystinuria	2021-07-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001356690	SCV005310806	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000611179	SCV000734089	benign	Classic homocystinuria		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000611179	SCV000745583	benign	Classic homocystinuria	2015-09-23	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000611179	SCV001461069	benign	Classic homocystinuria	2020-09-16	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356690	SCV001551929	uncertain significance	not provided		no assertion criteria provided	clinical testing	multiple AR variants in same gene - keep for nowAllele frequency is common in at least one population database (frequency: 62.069% in ExAC) based on the frequency threshold of 1.432% for this gene.Variant was observed in a homozygous state in population databases more than expected for disease.10 reputable source/s reports the variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.A synonymous variant not located in a splice region.
Clinical Genetics, Academic Medical Center	RCV000078107	SCV001918941	benign	not specified		no assertion criteria provided	clinical testing