Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985697 | SCV001134149 | uncertain significance | not provided | 2018-10-24 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002372706 | SCV002667385 | uncertain significance | Cystic fibrosis | 2014-08-04 | criteria provided, single submitter | clinical testing | The p.C225Y variant (also known as c.674G>A), located in coding exon 6 of the CFTR gene, results from a G to A substitution at nucleotide position 674. The cysteine at codon 225 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323774 | SCV004028753 | uncertain significance | not specified | 2023-07-14 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.674G>A (p.Cys225Tyr) results in a non-conservative amino acid change located in the transmembrane domain (IPR011527) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251420 control chromosomes (gnomAD v2.1, Exomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.674G>A has been not been reported in the literature in individuals affected with Chronic Pancreatitis, and has only been reported in unaffected carriers (e.g., Pagin_2016). This report therefore does not provide unequivocal conclusions about association of the variant with Chronic Pancreatitis Risk. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 26900683). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |