ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.670G>A (p.Glu224Lys)

gnomAD frequency: 0.00001  dbSNP: rs373121544
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596201 SCV000705746 uncertain significance not provided 2017-01-18 criteria provided, single submitter clinical testing
Counsyl RCV000671914 SCV000796948 uncertain significance Smith-Lemli-Opitz syndrome 2018-01-08 criteria provided, single submitter clinical testing
Invitae RCV000671914 SCV001203652 pathogenic Smith-Lemli-Opitz syndrome 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 224 of the DHCR7 protein (p.Glu224Lys). This variant is present in population databases (rs373121544, gnomAD 0.004%). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 15776424). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 499993). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DHCR7 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV000671914 SCV002093033 uncertain significance Smith-Lemli-Opitz syndrome 2020-02-25 no assertion criteria provided clinical testing

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