ClinVar Miner

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

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
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 absence of the vas deferens 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
Invitae RCV000822612 SCV000963422 uncertain significance Cystic fibrosis 2018-10-16 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.

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