Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004690911 | SCV005184491 | likely pathogenic | Vitamin D-dependent rickets, type 1A | 2024-05-31 | criteria provided, single submitter | clinical testing | Variant summary: CYP27B1 c.1376G>C (p.Arg459Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251430 control chromosomes. To our knowledge, no occurrence of c.1376G>C in individuals affected with Vitamin D-dependent rickets and no experimental evidence demonstrating its impact on protein function have been reported. A different variant affecting the same codon has been classified as pathogenic by our lab (c.1376G>T, p.Arg459Leu), and another is classified on the pathogenic spectrum in ClinVar (c.1375C>T,p.Arg459Cys) supporting the critical relevance of codon 459 to CYP27B1 protein function. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic. |