Submissions for variant NM_000071.3(CBS):c.924C>T (p.Tyr308=)

gnomAD frequency: 0.00003  dbSNP: rs149809170

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000862590	SCV000436213	uncertain significance	Classic homocystinuria	2018-01-12	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.
GeneDx	RCV001698128	SCV000526472	likely benign	not provided	2020-11-12	criteria provided, single submitter	clinical testing
Invitae	RCV002231052	SCV001003114	likely benign	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2024-01-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002374585	SCV002688303	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2022-01-20	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.
PreventionGenetics, part of Exact Sciences	RCV003932361	SCV004755029	likely benign	CBS-related disorder	2019-07-11	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).
Natera, Inc.	RCV000862590	SCV002083786	likely benign	Classic homocystinuria	2020-02-09	no assertion criteria provided	clinical testing