ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.874_875delinsTT (p.Glu292Leu) (rs1064795178)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482632 SCV000570729 uncertain significance not specified 2016-06-20 criteria provided, single submitter clinical testing The c.874_875delGAinsTT variant results in the deletion of two nucleotides and the insertion of two incorrect nucleotides, causing a substitution of Leucine for Glutamic acid at codon 292, denoted as p.Glu292Leu. The c.874_875delGAinsTT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This is variant results in a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. As an alternate mechanism, some splice predictor models indicate that this sequence change may strengthen a cryptic splice acceptor site downstream of the natural splice acceptor site of intron 9, which may result in abnormal gene splicing. We interpret c.874_875delGAinsTT as a variant of uncertain significance.

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