ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1364C>T (p.Ala455Val) (rs74551128)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474081 SCV000552139 uncertain significance Cystic fibrosis 2016-12-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 455 of the CFTR protein (p.Ala455Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs74551128, ExAC 0.02%). This variant has been reported in an individual who underwent CFTR testing (PMID: 15371908). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Ala455Glu) has been determined to be pathogenic (PMID: 23974870). This suggests that the alanine residue is critical for CFTR protein function and that other missense substitutions at this position may also be pathogenic. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000729714 SCV000857400 uncertain significance not provided 2017-10-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000729714 SCV000889281 uncertain significance not provided 2017-12-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001011136 SCV001171424 likely pathogenic Inborn genetic diseases 2019-03-19 criteria provided, single submitter clinical testing 2 of classification of c (below) met (2c = 1b);In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Other strong data supporting pathogenic classification ;Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes)

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