ClinVar Miner

Submissions for variant NM_001360.2(DHCR7):c.1138T>C (p.Cys380Arg) (rs373306653)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725474 SCV000337184 likely pathogenic not provided 2018-03-30 criteria provided, single submitter clinical testing
Invitae RCV000408382 SCV000945509 likely pathogenic Smith-Lemli-Opitz syndrome 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 380 of the DHCR7 protein (p.Cys380Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is present in population databases (rs373306653, ExAC 0.002%). This variant has been observed in several individuals affected with DHCR7-related conditions (PMID: 15896653, 17441222). ClinVar contains an entry for this variant (Variation ID: 284527). 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"). This variant disrupts the p.Cys380 amino acid residue in DHCR7. Other variants that disrupt this residue have been observed in affected individuals (PMID: 10677299, 20014133, 9653161), 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Counsyl RCV000408382 SCV000796081 likely pathogenic Smith-Lemli-Opitz syndrome 2017-12-01 no assertion criteria provided clinical testing

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