ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.1163C>T (p.Thr388Met) (rs143860237)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590683 SCV000696822 uncertain significance not provided 2016-07-13 criteria provided, single submitter clinical testing Variant summary: The CFTR c.1163C>T (p.Thr388Met) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a damaging outcome. This variant was found in 16/119226 control chromosomes at a frequency of 0.0001342, which does not exceed the estimated maximal expected allele frequency of a pathogenic CFTR variant (0.0129603). This variant has been reported via literatures in patients with asthma, CBAVD, or CF without strong evidence for causality. CF mutation db lists variant found in a Jordanian CF patient who is PI with no additional clinical and genotype information available. Taken together, because of the lack of clinical information and the absence of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000590683 SCV000855815 uncertain significance not provided 2017-07-25 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765924 SCV000897344 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
Invitae RCV000822612 SCV000963422 uncertain significance Cystic fibrosis 2019-08-21 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 388 of the CFTR protein (p.Thr388Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs143860237, ExAC 0.03%). This variant has been observed in an individual affected with cystic fibrosis and in an another affected with congenital bilateral absence of the vas deferens (PMID: 26708955, 15070876). It has also been observed in an individual with asthma (PMID: 11354633). This variant is also known as c.1295C>T in the literature. ClinVar contains an entry for this variant (Variation ID: 495887). 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 methionine 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. 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.
Mendelics RCV000822612 SCV001137473 likely benign Cystic fibrosis 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010062 SCV001170206 uncertain significance Inborn genetic diseases 2019-08-13 criteria provided, single submitter clinical testing The p.T388M variant (also known as c.1163C>T), located in coding exon 9 of the CFTR gene, results from a C to T substitution at nucleotide position 1163. The threonine at codon 388 is replaced by methionine, an amino acid with similar properties. This variant was first reported in an individual with cystic fibrosis (CF) and pancreatic insufficiency (Zielenski J et al. Cystic Fibrosis Mutation Database [database online] Toronto, ON, Canada: SickKids; 5-23-96); however, a second CFTR alteration was not identified. This variant was also reported in one individual with asthma, normal sweat chloride levels, and no classic symptoms of CF (Tzetis M et al. Hum. Genet. 2001 Mar; 108(3):216-21). In addition, this variant has been seen in one individual with a clinical diagnosis of congenital bilateral absence of the vas deferens (CBAVD) who did not have a second CFTR alteration (Dayangaç D et al. Hum. Reprod. 2004 May; 19(5):1094-100). This amino acid position is well conserved in available vertebrate species; however, methionine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on available evidence to date, the clinical significance of this alteration remains unclear.
Illumina Clinical Services Laboratory,Illumina RCV001158655 SCV001320307 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001287349 SCV001474024 uncertain significance none provided 2020-03-20 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000590683 SCV001714232 uncertain significance not provided 2019-12-17 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000822612 SCV001737257 uncertain significance Cystic fibrosis 2021-05-18 criteria provided, single submitter clinical testing

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