Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV002465059 | SCV002759454 | likely pathogenic | Cholestanol storage disease | 2022-09-20 | criteria provided, single submitter | clinical testing | This variant was identified as a part of carrier screening. The c.379C>G variant is not present in publicly available population databases such as 1000 Genomes, EVS, Indian Exome Database or in our in-house exome database. The variant is present in ExAC and gnomAD at a low frequency. This variant has neither been published in literature nor reported to the ClinVar, Human Genome Mutation Database (HGMD) or OMIM databases, in any affected individuals. An alternative variant (c.379C>T, Arg127Trp) in this position has been previously observed in affected individuals, published several times and reported to clinvar (Accession ID: VCV000065865.22) and HGMD (ID: CM994442) as ‘pathogenic’. In-silico pathogenicity prediction programs like SIFT, Polyphen2, MutationTaster2, CADD etc. predicted this variant to be likely deleterious. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002465059 | SCV005076403 | likely pathogenic | Cholestanol storage disease | 2024-04-26 | criteria provided, single submitter | clinical testing | Variant summary: CYP27A1 c.379C>G (p.Arg127Gly) 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 4e-06 in 251374 control chromosomes. c.379C>G has been reported in the literature in at least one homozygous individuals affected with Cerebrotendinous Xanthomatosis (e.g. Shaji_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A different variant located at the same codon (c.379C>T, p.Arg127Trp) has been classified as pathogenic, supporting a critical relevance of this residue to CYP27A1 protein function. The following publication has been ascertained in the context of this evaluation (PMID: 31736580). ClinVar contains an entry for this variant (Variation ID: 1802246). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002465059 | SCV005647732 | likely pathogenic | Cholestanol storage disease | 2024-05-07 | criteria provided, single submitter | clinical testing |