Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174738 | SCV001338044 | uncertain significance | not specified | 2023-08-11 | criteria provided, single submitter | clinical testing | Variant summary: CFTR c.980T>G (p.Leu327Arg) results in a non-conservative amino acid change located in the first transmembrane domain (IPR011527) of 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 1.6e-05 in 251290 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.980T>G has been reported in the literature in a family where 2 individuals carrying the variant were affected with Chronic Pancreatitis, and a third family member who didn't carry the variant was unaffected, however only 2 variants in the PRSS1 gene were tested, and other genes associated with chronic pancreatitis risk were not tested (Ravnik-Glavac_1996, Ravnik-Glavac_2000). Therefore these reports do 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 publications have been ascertained in the context of this evaluation (PMID: 10909845, 8992448, 10653140, 11276378). Four ClinVar submitters have assessed the variant since 2014, and all submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV001241079 | SCV001414071 | uncertain significance | Cystic fibrosis | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with arginine at codon 327 of the CFTR protein (p.Leu327Arg). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and arginine. This variant is present in population databases (rs141115171, ExAC 0.004%). This missense change has been observed in individual(s) with hereditary pancreatitis (PMID: 8992448). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Genome- |
RCV001241079 | SCV002027383 | uncertain significance | Cystic fibrosis | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001241079 | SCV002689600 | uncertain significance | Cystic fibrosis | 2022-03-23 | criteria provided, single submitter | clinical testing | The p.L327R variant (also known as c.980T>G), located in coding exon 8 of the CFTR gene, results from a T to G substitution at nucleotide position 980. The leucine at codon 327 is replaced by arginine, an amino acid with dissimilar properties. Co-segregation was reported in a family with hereditary pancreatitis in two affected individuals, and the alteration was not detected in one unaffected individual (Ravnik-Glavac M, Pflugers Arch. 1996 ; 431(6 Suppl 2):R191-2; Ravnik-Glavac et al. Pflugers Arch. 2000 ;439(3 Suppl):R50-2). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001828586 | SCV002078171 | uncertain significance | CFTR-related disorders | 2018-05-12 | no assertion criteria provided | clinical testing |