ClinVar Miner

Submissions for variant NM_000492.4(CFTR):c.3746G>A (p.Gly1249Glu) (rs121909040)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000007637 SCV000886364 uncertain significance Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
CFTR-France RCV000007637 SCV001169363 pathogenic Cystic fibrosis 2018-01-29 criteria provided, single submitter curation
Invitae RCV000007637 SCV001505750 uncertain significance Cystic fibrosis 2020-07-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 1249 of the CFTR protein (p.Gly1249Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 8880589, 7520022). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 7216). 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.
OMIM RCV000007637 SCV000027838 pathogenic Cystic fibrosis 1994-07-01 no assertion criteria provided literature only

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