Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV002254396 | SCV002525539 | likely pathogenic | Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation | 2022-04-20 | criteria provided, single submitter | clinical testing | The c.1825C>T variant is not present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) and Indian Exome Database. The variant is not present in our in-house exome database. The variant was not previously reported to Clinvar, Human Genome Mutation Database (HGMD) and/or OMIM databases, in any affected individuals. In-silico pathogenicity prediction programs like PolyPhen-2, MutationTaster2, CADD, Varsome etc. predicted this variant to be likely deleterious. The variant is present in a mutational hotspot region of the CFTR gene and an alternative variant in the same amino acid position (His609Arg) was earlier published several times and reported to ClinVar as pathogenic (Accession: VCV000053398.10). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004587335 | SCV005076990 | uncertain significance | not specified | 2024-04-23 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.1825C>T (p.His609Tyr) results in a conservative amino acid change located in the ABC transporter-like, ATP-binding domain (IPR003439) of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 232284 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1825C>T in individuals affected with Cystic Fibrosis 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.1826A>G, p.His609Arg), supporting as possible critical relevance of codon 609 to CFTR protein function. ClinVar contains an entry for this variant (Variation ID: 1691298). Based on the evidence outlined above, the variant was classified as uncertain significance. |