ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.50dup (p.Ser18fs) (rs397508714)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001060 SCV001158181 pathogenic not specified 2019-02-11 criteria provided, single submitter clinical testing The CFTR c.50dupT; p.Ser18fs variant (rs397508714), also known as 43_44insT or 175insT for legacy nomenclature, is reported in the SickKids database (see link). This variant also contains an entry in the ClinVar database (Variation ID: 53944). It is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by duplicating a single nucleotide, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Additionally, a different frameshift variant at this position (c.50delT, also known as 182delT) is reported in the CFTR2 database and is commonly associated with pancreatic insufficient cystic fibrosis (CFTR2 database). Based on available information, the c.50dupT variant is considered to be pathogenic. REFERENCES CFTR2 database: Link to SickKids CFTR database:
Integrated Genetics/Laboratory Corporation of America RCV000577158 SCV001337845 pathogenic Cystic fibrosis 2020-01-23 criteria provided, single submitter clinical testing Variant summary: CFTR c.50dupT (p.Ser18GlnfsX27) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250742 control chromosomes (gnomAD). c.50dupT (also described in the literature as 175insT) has been reported in multiple homozygous and compound heterozygous individuals affected with Cystic Fibrosis and related phenotypes (Schaedel_1995, Schaedel_1999, Ge_2019). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI) RCV000577158 SCV000679139 not provided Cystic fibrosis no assertion provided literature only

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