Submissions for variant NM_000071.3(CBS):c.313C>G (p.Leu105Val)

dbSNP: rs1601375543

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002233864	SCV000933711	uncertain significance	HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED	2021-08-27	criteria provided, single submitter	clinical testing	This sequence change replaces leucine with valine at codon 105 of the CBS protein (p.Leu105Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with cystathionine beta-synthase deficiency (PMID: 10338090). This variant is also known as g.3680C>G c.313del4. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Child Health and Human Development Program, Research Institute of the McGill University Health Center	RCV000794312	SCV001424671	pathogenic	Classic homocystinuria		no assertion criteria provided	clinical testing	The c.313C>G (L105V) was identified in a patient of French Canadian origin in compound heterozygote with c.676G>A (A226T). Clinical characteristics included lens dislocation and elevated fasting homocysteine. Patient had no intellectual impairment and responds to treatment with vitamin B6.