ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.682C>T (p.Arg228Trp) (rs775773057)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674773 SCV000800167 uncertain significance Smith-Lemli-Opitz syndrome 2018-05-23 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000674773 SCV000894666 uncertain significance Smith-Lemli-Opitz syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000674773 SCV001415982 pathogenic Smith-Lemli-Opitz syndrome 2020-10-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 228 of the DHCR7 protein (p.Arg228Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs775773057, ExAC 0.003%). This variant has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 15776424, 22226660). 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: 558494). 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. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001267993 SCV001446554 likely pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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