ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.740C>T (p.Ala247Val) (rs886041354)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000383910 SCV000329857 pathogenic not provided 2017-12-08 criteria provided, single submitter clinical testing The A247V has also been reported in association with SLOS in several unrelated individuals who were also heterozygous for another pathogenic variant in the DHCR7 gene (Fitzky et al., 1998; Balogh et al., 2012; Sparks et al., 2014). We consider this variant to be pathogenic.
Counsyl RCV000670451 SCV000795305 likely pathogenic Smith-Lemli-Opitz syndrome 2017-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000670451 SCV001163700 pathogenic Smith-Lemli-Opitz syndrome criteria provided, single submitter clinical testing
Invitae RCV000670451 SCV001203581 pathogenic Smith-Lemli-Opitz syndrome 2019-04-17 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 247 of the DHCR7 protein (p.Ala247Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with Smith Lemli Opitz syndrome (PMID: 9653161, 10995508, 15896653). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 280065). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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.