ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.907G>T (p.Gly303Trp) (rs142808899)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000794082 SCV000933468 uncertain significance Smith-Lemli-Opitz syndrome 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with tryptophan at codon 303 of the DHCR7 protein (p.Gly303Trp). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and tryptophan. This variant is present in population databases (rs142808899, ExAC 0.006%). This variant has not been reported in the literature in individuals with DHCR7-related conditions. 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 and their clinical significance is uncertain. This variant disrupts the p.Gly303 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been observed in individuals with DHCR7-related conditions (PMID: 16044199, 20052364, 28503313), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera Inc RCV000794082 SCV001190685 likely pathogenic Smith-Lemli-Opitz syndrome 2019-05-20 no assertion criteria provided clinical testing

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