ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.976G>T (p.Val326Leu) (rs80338859)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000007187 SCV000677991 pathogenic Smith-Lemli-Opitz syndrome 2015-06-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000007187 SCV000697860 pathogenic Smith-Lemli-Opitz syndrome 2017-05-22 criteria provided, single submitter clinical testing Variant summary: The DHCR7 c.976G>T (p.Val326Leu) variant involves the alteration of a conserved nucleotide and 3/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome. This variant was found in 5/104104 control chromosomes at a frequency of 0.000048, which does not exceed the estimated maximal expected allele frequency of a pathogenic DHCR7 variant (0.0043301). Multiple publications have cited the variant in homozygous and compound heterozygous affected individuals. Authors have also indicated the variant to be a common mutation (Ciara_2004). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000007187 SCV000835626 pathogenic Smith-Lemli-Opitz syndrome 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 326 of the DHCR7 protein (p.Val326Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs80338859, ExAC 0.02%). This variant has been observed in combination with other pathogenic variants in several individuals affected with Smith–Lemli–Opitz syndrome (PMID: 9653161, 15521979, 27513191). ClinVar contains an entry for this variant (Variation ID: 6785). Experimental studies have shown that this missense change drastically reduces DHCR7 protein expression (PMID: 9653161). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000007187 SCV000893241 pathogenic Smith-Lemli-Opitz syndrome 2018-10-31 criteria provided, single submitter clinical testing
OMIM RCV000007187 SCV000027383 pathogenic Smith-Lemli-Opitz syndrome 2004-12-01 no assertion criteria provided literature only
GeneReviews RCV000007187 SCV000040856 pathologic Smith-Lemli-Opitz syndrome 2007-10-24 no assertion criteria provided curation Converted during submission to Pathogenic.

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