ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.1190C>T (p.Ser397Leu) (rs773134475)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000716033 SCV000846866 likely pathogenic History of neurodevelopmental disorder 2016-06-20 criteria provided, single submitter clinical testing Detected in individual(s) satisfying established diagnostic criteria for classic disease in trans with a mutation or mutation is homozygous;Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes) ;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Invitae RCV000805883 SCV000945858 pathogenic Smith-Lemli-Opitz syndrome 2019-10-17 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 397 of the DHCR7 protein (p.Ser397Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs773134475, ExAC 0.002%). This variant has been observed on the opposite chromosome (in trans) from other pathogenic variants in individuals affected with Smith-Lemli-Opitz Syndrome (PMID: 15521979, 23293579, 22211794, 10677299). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.

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