Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000001726 | SCV004037925 | likely pathogenic | Vitamin D-dependent rickets, type 1A | 2023-08-02 | criteria provided, single submitter | clinical testing | Variant summary: CYP27B1 c.374G>A (p.Gly125Glu) results in a non-conservative amino acid change in the encoded protein sequence. This alters a conserved residue (HGMD) in which another missense variant (p.Gly125Arg) has been classified as likely pathogenic by a ClinVar submitters, suggesting this may be a functionally important amino acid. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 177120 control chromosomes (gnomAD). c.374G>A has been reported in the literature in a homozygous individual affected with pseudovitamin D-dependent rickets (Kitanaka_1998). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant protein had no 1alpha-hydroxylase activity (Kitanaka_1998). The following publication has been ascertained in the context of this evaluation (PMID: 9486994). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000001726 | SCV000021882 | pathogenic | Vitamin D-dependent rickets, type 1A | 1998-03-05 | no assertion criteria provided | literature only |