Submissions for variant NM_000071.3(CBS):c.816T>A (p.Cys272Ter)

dbSNP: rs528689432

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000507871	SCV000602924	likely pathogenic	not provided	2017-05-29	criteria provided, single submitter	clinical testing	The p.Cys272Ter variant (rs528689432) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. The c.816T>A variant creates a termination codon in the CBS protein at position 272 in exon 9 which is predicted to result in a truncated or absent protein product. It is absent from general population databases such as 1000 Genomes, NHLBI GO Exome Sequencing Project (ESP), and the Exome Aggregation Consortium (ExAC) browser. Based on these observations the p.Cys272Ter variant has been classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002231187	SCV001211240	pathogenic	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2023-08-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 439461). This variant has not been reported in the literature in individuals affected with CBS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys272*) in the CBS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CBS are known to be pathogenic (PMID: 10338090, 12124992).
GeneDx	RCV000507871	SCV001789568	likely pathogenic	not provided	2024-05-17	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease
Baylor Genetics	RCV000673238	SCV004215560	likely pathogenic	Classic homocystinuria	2023-12-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000507871	SCV005093631	pathogenic	not provided	2024-07-01	criteria provided, single submitter	clinical testing	CBS: PVS1, PM2, PP4:Moderate
Counsyl	RCV000673238	SCV000798419	likely pathogenic	Classic homocystinuria	2018-03-05	no assertion criteria provided	clinical testing