ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.794T>G (p.Met265Arg) (rs148519623)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506843 SCV000603052 uncertain significance not specified 2017-03-05 criteria provided, single submitter clinical testing
Counsyl RCV000671208 SCV000796161 uncertain significance Cystic fibrosis 2017-12-04 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000506843 SCV000917193 likely pathogenic not specified 2018-03-27 criteria provided, single submitter clinical testing Variant summary: CFTR c.794T>G (p.Met265Arg) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.5e-05 in 271396 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in CFTR causing CFTR-related diseases (1.5e-05 vs 0.013), allowing no conclusion about variant significance. c.794T>G has been reported in the literature in individuals affected with CFTR-related diseases (Dork 1997, Goossens 2000). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function (Okiyoneda 2013). The most pronounced variant effect results in <10% of normal activity. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. As of now, there are 7 patients with this variant in the CFTR2 database and it was annotated as a variant with varying clinical consequences, i.e. some patients with this variant, combined with another CF-causing variant, have CF, while other patients do not have CF. Because of this variability, it is very important that clinical criteria alone be used to determine whether a person with this variant has CF. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV001004238 SCV001163114 pathogenic Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation criteria provided, single submitter clinical testing

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