ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.970T>C (p.Tyr324His) (rs1173707321)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000525900 SCV000630078 pathogenic Smith-Lemli-Opitz syndrome 2017-03-07 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 324 of the DHCR7 protein (p.Tyr324His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals with a clinical diagnosis of Smith-Lemli-Opitz syndrome (SLOS; PMID: 10677299). It also occurs with a pathogenic (c.964-1G>C) or a second rare (p.Gly322Arg) variant in DHCR7 in 2 individuals with SLOS  and elevated serum 7-dehydrocholesterol levels (PMID: 10814720, 22438180). While it is unknown if the variant is on the same or opposite chromosomes as the other variants in these individuals, this observation suggests the c.970T>C substitution may contribute to the cause of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000525900 SCV000793925 uncertain significance Smith-Lemli-Opitz syndrome 2017-09-12 criteria provided, single submitter clinical testing

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