ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.944T>C (p.Phe315Ser) (rs760319837)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000589384 SCV000883577 uncertain significance not provided 2017-12-13 criteria provided, single submitter clinical testing The CFTR c.944T>C; p.Phe315Ser variant is reported in the medical literature in one individual with CFTR-related metabolic disorder (Prach 2013). The variant is listed in the dbSNP variant database (rs760319837) and in the Genome Aggregation Database in 45/277018 alleles, but is not listed in the ClinVar database. The phenylalanine at this position is conserved across species and computational algorithms (PolyPhen2, SIFT) predict this variant is deleterious. Considering available information, there is insufficient evidence to classify this variant with certainty. References: Prach L et al. Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California. J Mol Diagn. 2013 Sep;15(5):710-22.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000589384 SCV000856956 uncertain significance not provided 2017-09-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589384 SCV000697059 uncertain significance not provided 2016-06-16 criteria provided, single submitter clinical testing Variant summary: The CFTR c.944T>C (p.Phe315Ser) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 18/121182 control chromosomes at a frequency of 0.0001485, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). It was reported in a childhood onset CFTR-related Metabolic syndrome patient, however without strong evidence for pathogenicity. Studies describing the impact the variant may have on the function of the protein were not published at the time of classification. Because of the absence of stronger clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000554519 SCV000625757 uncertain significance Cystic fibrosis 2018-07-23 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with serine at codon 315 of the CFTR protein (p.Phe315Ser). The phenylalanine residue is moderately conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is present in population databases (rs760319837, ExAC 0.2%). This variant has been reported in an individual affected with CFTR-related metabolic syndrome (PMID: 23810505). ClinVar contains an entry for this variant (Variation ID: 455784). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.

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