ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.137C>T (p.Ala46Val)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000728272 SCV000855825 uncertain significance not provided 2018-09-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780112 SCV000917156 uncertain significance not specified 2017-09-22 criteria provided, single submitter clinical testing Variant summary: The c.137C>T (p.Ala46Val) in CFTR gene is a missense variant involves a highly conserved nucleotide and 5/5 in silico tools predict deleterious outcome, however no functional studies supporting these predictions were published at the time of evaluation. The c.137C>T is present in the control population datasets of ExAC and gnomAD at a low frequency of 0.00004 (5/119380 and 14/ 276484 chrs tested, respectively, exclusively in African subpopulation). The observed frequency does not exceed the maximum expected allele frequency for a pathogenic variant of 0.0129, suggesting that it is not a common polymorphism. To our knowledge, the variant has not been reported in affected individuals via peer-reviewed reports, but is mentioned to be identified in at least one affected individual with positive newborn screen test, who also carried F508del (phase is unknown). In addition, alteration of the same codon, c.137C>A (p.Ala46Asp) has been identified in Cf-patients and is reported as pathogenic by several laboratories, including CFTR.org. However, the variant of interest, c.137C>T is cited as VUS by reputable databases/clinical laboratories. Taken together, due to the lack of supportive evidence, the variant was classified as VUS, until new information becomes available.
Mendelics RCV000757789 SCV000886163 likely pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing

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