ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.4027G>A (p.Gly1343Ser) (rs747324955)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587884 SCV000697001 uncertain significance not provided 2016-06-16 criteria provided, single submitter clinical testing Variant summary: The CFTR c.4027G>A (p.Gly1343Ser) 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 7/121332 control chromosomes at a frequency of 0.0000577, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of 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 RCV000698058 SCV000826699 uncertain significance Cystic fibrosis 2018-11-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 1343 of the CFTR protein (p.Gly1343Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs747324955, ExAC 0.01%). This variant has not been reported in the literature in individuals with CFTR-related disease. 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 disruptive, 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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