Submissions for variant NM_000071.3(CBS):c.133C>T (p.Arg45Trp)

gnomAD frequency: 0.00013  dbSNP: rs201372812

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000198945	SCV000249718	likely benign	not provided	2020-04-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002229027	SCV000555953	likely benign	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2025-01-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000198945	SCV001247531	uncertain significance	not provided	2019-11-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002381662	SCV002692736	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-03-22	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004767135	SCV005380623	likely benign	not specified	2024-08-12	criteria provided, single submitter	clinical testing	Variant summary: CBS c.133C>T (p.Arg45Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00066 in 250626 control chromosomes, including one homozygote, and predominantly at a frequency of 0.0041 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in CBS causing Homocystinuria phenotype (0.003). To our knowledge, no occurrence of c.133C>T in individuals affected with Homocystinuria and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 212871). Based on the evidence outlined above, the variant was classified as likely benign.
Natera, Inc.	RCV001081627	SCV001460091	likely benign	Classic homocystinuria	2019-12-29	no assertion criteria provided	clinical testing