ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1519A>G (p.Ile507Val) (rs1801178)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169215 SCV000220474 likely benign Cystic fibrosis 2014-07-02 criteria provided, single submitter literature only
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755926 SCV000883603 likely benign not provided 2017-10-01 criteria provided, single submitter clinical testing
Mendelics RCV000169215 SCV001137479 benign Cystic fibrosis 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000169215 SCV001422196 uncertain significance Cystic fibrosis 2019-10-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 507 of the CFTR protein (p.Ile507Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs1801178, ExAC 0.006%). This variant has been observed in individuals with clinical features of cystic fibrosis and congenital absence of the vas deferens (PMID: 16714368, 23857699, 29124052). ClinVar contains an entry for this variant (Variation ID: 188863). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Ile507Phe amino acid residue in CFTR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23974870, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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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