ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.531G>C (p.Lys177Asn) (rs1064795022)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478922 SCV000570413 uncertain significance not provided 2016-05-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CBS gene. The c.531 G>C (K177N) variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was also not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.At the nucleotide level, c.531 G>C (K177N) occurs in the last nucleotide position in the exon, which may play a role in splicing. This substitution occurs at a nucleotide position that is not conserved, though cytosine is not the native nucleotide at this site in any species. In silico splice prediction programs predict this variant results in the loss/reduced efficiency of the splice donor site in intron 6 of the CBS gene. In the absence of functional mRNA studies, the physiological consequence of this variant on splicing cannot be precisely determined. At the protein level, c.531 G>C (K177N) is a semi-conservative amino acid substitution. As these residues share similar properties, but differ in size, charge, or other properties, it may impact secondary structure. This missense substitution occurs at an amino acid position that is conserved and in silico analysis predicts this variant is probably damaging to the protein structure/function.Therefore, based on the currently available information, it is unclear whether this a pathogenic or rare benign variant.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.