Submissions for variant NM_000071.3(CBS):c.954G>A (p.Thr318=)

dbSNP: rs776122644

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002552594	SCV001210328	uncertain significance	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2021-06-30	criteria provided, single submitter	clinical testing	This sequence change affects codon 318 of the CBS mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CBS protein. This variant also falls at the last nucleotide of exon 10 of the CBS coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs776122644, ExAC 0.002%). This variant has not been reported in the literature in individuals with CBS-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV003311934	SCV004011364	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	CBS: PM2:Supporting, BP4, BP7
Natera, Inc.	RCV001046424	SCV001462110	uncertain significance	Classic homocystinuria	2020-09-16	no assertion criteria provided	clinical testing