ClinVar Miner

Submissions for variant NM_001360.3(DHCR7):c.433A>C (p.Ile145Leu)

dbSNP: rs1555146475
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674923 SCV000800339 uncertain significance Smith-Lemli-Opitz syndrome 2018-06-04 criteria provided, single submitter clinical testing
Invitae RCV000674923 SCV001382270 pathogenic Smith-Lemli-Opitz syndrome 2023-03-29 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DHCR7 protein function. ClinVar contains an entry for this variant (Variation ID: 558625). This missense change has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 15954111, 20556518). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 145 of the DHCR7 protein (p.Ile145Leu).
DASA RCV000674923 SCV002526395 pathogenic Smith-Lemli-Opitz syndrome 2022-06-10 criteria provided, single submitter clinical testing The c.433A>C;p.(Ile145Leu) missense change has been observed in affected individual(s) (PMID: 20556518; 15954111; 30925529) - PS4. This variant is not present in population databases:rs1555146475, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The p.(Ile145Leu) was detected in trans with a Pathogenic variant (PMID: 20556518; 15954111; 30925529) - PM3_strong. The variant co-segregated with disease in multiple affected family members (PMID: 30925529) - PP1. In summary, the currently available evidence indicates that the variant is Pathogenic

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