ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.418C>T (p.Pro140Ser) (rs145900055)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506712 SCV000601118 uncertain significance not specified 2017-01-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590469 SCV000697011 uncertain significance not provided 2017-06-21 criteria provided, single submitter clinical testing Variant summary: The CFTR c.418C>T (p.Pro140Ser) variant involves the alteration of a conserved nucleotide, resulting in a missense change in the ABC transporter type 1, transmembrane domain (InterPro). 4/4 in silico tools predict damaging outcome for this variant. This variant was found in control population (including ExAC) at a frequency of 0.0000681 (9/132142 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant was found in one patient with disseminated bronchiectasis (Sick Kids database) and one CF patient (Schrijver_2016) without strong evidence for or against pathogenicity. It has been classified in the literature as a variant of uncertain significance (Monaghan_2004; Audrezet_2008). One clinical diagnostic laboratory (in ClinVar) has reported identifying this variant, though a classification was not provided. Another missense change at the same residue (P140L) has been reported in association with CF in literature and/or clinical databases. Taken together, this variant is classified as VUS until additional information becomes available.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000590469 SCV000704520 uncertain significance not provided 2017-10-11 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765922 SCV000897342 uncertain significance Bronchiectasis with or without elevated sweat chloride 1; Cystic fibrosis; Hereditary pancreatitis; Congenital bilateral aplasia of vas deferens from CFTR mutation 2018-10-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506712 SCV001158528 uncertain significance not specified 2019-06-03 criteria provided, single submitter clinical testing The CFTR c.418C>T; p.Pro140Ser variant (rs145900055) is reported in the literature in an individual affected with cystic fibrosis and another individual with disseminated bronchiectasis, though it was not demonstrated to be disease-causing (Schrijver 2016, SickKids CFTR database). This variant is found in the general population with an overall allele frequency of 0.02% (43/282098 alleles) in the Genome Aggregation Database, and it is reported in ClinVar (Variation ID: 53912). The proline at codon 140 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Pro140Ser variant is uncertain at this time. References: SickKids CFTR database: http://www.genet.sickkids.on.ca/ Schrijver I et al. The Spectrum of CFTR Variants in Nonwhite Cystic Fibrosis Patients: Implications for Molecular Diagnostic Testing. J Mol Diagn. 2016 Jan;18(1):39-50.
Ambry Genetics RCV001022010 SCV001183697 uncertain significance Inborn genetic diseases 2019-02-14 criteria provided, single submitter clinical testing Insufficient evidence
Illumina Clinical Services Laboratory,Illumina RCV001163274 SCV001325297 uncertain significance CFTR-related disorders 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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