ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.365A>G (p.Tyr122Cys) (rs377295859)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471538 SCV000552134 uncertain significance Cystic fibrosis 2018-07-10 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 122 of the CFTR protein (p.Tyr122Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs377295859, ExAC 0.002%). This variant has been observed as homozygous in an individual affected with chronic pancreatitis (PMID: 19812525). ClinVar contains an entry for this variant (Variation ID: 411120). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Integrated Genetics/Laboratory Corporation of America RCV000586920 SCV000696980 uncertain significance not provided 2016-01-21 criteria provided, single submitter clinical testing Variant summary: CFTR c.365A>G affects a conserved nucleotide, resulting in amino acid change from Tyr to Cys. 5/5 in-silico tools predict damaging outcome for this variant, however these predictions have not been verified with functional studies. This variant is found in 1/120558 control chromosomes at a frequency of 0.0000083, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0129603). The variant has been cited in 1 homozygous individual with alcoholic etiology of chronic pancreatitis (ACP) without evidence of causation (ie co-segregation). Because of the absence of significant clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.

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