Submissions for variant NM_000071.3(CBS):c.969G>A (p.Trp323Ter)

dbSNP: rs863223432

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000197013	SCV000249697	pathogenic	not provided	2015-06-11	criteria provided, single submitter	clinical testing	The W323X nonsense mutation in the CBS gene has been reported previously in association with homocystinuria due to cystathionine beta synthase (CBS) deficiency (Zaidi et al., 2012). W323X appears to be a common mutation in Saudi Arabian patients having been found in 10 of 13 Saudi Arabian families with homocystinuria due to CBS deficiency (Zaidi et al., 2012). Furthermore, this mutation is located in the catalytic domain of the CBS protein (Zaidi et al., 2012) and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. This variant was found in CBS
Eurofins Ntd Llc (ga)	RCV000197013	SCV000330914	pathogenic	not provided	2015-11-20	criteria provided, single submitter	clinical testing
Counsyl	RCV000363392	SCV000789412	pathogenic	Classic homocystinuria	2017-02-07	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000363392	SCV001520269	pathogenic	Classic homocystinuria	2019-07-17	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae	RCV003495115	SCV004297406	pathogenic	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2023-11-06	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp323*) 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). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with homocystinuria (PMID: 21517828, 29352562). ClinVar contains an entry for this variant (Variation ID: 212856). For these reasons, this variant has been classified as Pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000363392	SCV004805170	likely pathogenic	Classic homocystinuria	2024-03-17	criteria provided, single submitter	research
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	RCV000363392	SCV000891630	pathogenic	Classic homocystinuria	2017-12-30	no assertion criteria provided	curation
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000363392	SCV001469293	pathogenic	Classic homocystinuria	2020-10-11	no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV000363392	SCV003927840	pathogenic	Classic homocystinuria	2023-04-01	no assertion criteria provided	clinical testing