ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.2684G>C (p.Ser895Thr) (rs201864483)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001000698 SCV001157737 uncertain significance not specified 2018-07-11 criteria provided, single submitter clinical testing The CFTR c.2684G>C; p.Ser895Thr variant (rs201864483), has not been reported in the literature in individuals affected with cystic fibrosis or pancreatits, but it has been observed in an unaffected control individual (Le Marechal 2001). This variant is found in the non-Finnish European population with an overall allele frequency of 0.00095% (12/126606 alleles) in the Genome Aggregation Database. The serine at codon 895 is weakly conserved and occurs as a threonine in several vertebrate species. Computational analyses (SIFT, PolyPhen-2) further predict that this variant is tolerated. However, due to limited information, the clinical significance of the p.Ser895Thr variant is uncertain at this time. References: Le Marechal C et al. Complete and rapid scanning of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by denaturing high-performance liquid chromatography (D-HPLC): major implications for genetic counselling. Hum Genet. 2001 Apr;108(4):290-8.
Invitae RCV001055324 SCV001219711 uncertain significance Cystic fibrosis 2019-11-12 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 895 of the CFTR protein (p.Ser895Thr). The serine residue is weakly conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs201864483, ExAC 0.009%). This variant has not been reported in the literature in individuals with CFTR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Illumina Clinical Services Laboratory,Illumina RCV001158766 SCV001320421 uncertain significance CFTR-related disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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