ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.1210C>A (p.Arg404Ser)

dbSNP: rs61757582
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668128 SCV000792679 uncertain significance Smith-Lemli-Opitz syndrome 2017-07-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000668128 SCV004294114 likely pathogenic Smith-Lemli-Opitz syndrome 2022-11-01 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Arg404 amino acid residue in DHCR7. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9653161, 10677299, 12818773, 15896653). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 552797). This missense change has been observed in individual(s) with clinical features of DHCR7-related conditions (PMID: 10677299, 10814720, 33578785). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 404 of the DHCR7 protein (p.Arg404Ser).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000668128 SCV005205268 likely pathogenic Smith-Lemli-Opitz syndrome 2024-06-05 criteria provided, single submitter clinical testing Variant summary: DHCR7 c.1210C>A (p.Arg404Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 241396 control chromosomes. c.1210C>A has been reported in the literature in individuals affected with Smith-Lemli-Opitz Syndrome (e.g. Witsch-Baumgartner_2000, Yu_2000, Zaidi_2021). These data indicate that the variant may be associated with disease. A different variant affecting the same codon has been classified as pathogenic by our lab (c.1210C>T, p.Arg404Cys), supporting the critical relevance of codon 404 to DHCR7 protein function. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 552797). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000668128 SCV005630294 likely pathogenic Smith-Lemli-Opitz syndrome 2024-06-06 criteria provided, single submitter clinical testing

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