ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3468G>A (p.Leu1156=) (rs139729994)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CFTR2 RCV000046899 SCV000677604 pathogenic Cystic fibrosis 2017-03-17 reviewed by expert panel research
Counsyl RCV000046899 SCV000220434 likely pathogenic Cystic fibrosis 2014-06-19 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000428306 SCV000227776 uncertain significance not provided 2014-12-11 criteria provided, single submitter clinical testing
GeneDx RCV000428306 SCV000521024 pathogenic not provided 2019-03-22 criteria provided, single submitter clinical testing The c.3468G>A (L1156L) variant has been previously reported to cause skipping of exon 21 (referred to as exon 18) in one proband with another pathogenic F508del allele; however, a full publication presenting this data is not available (Zielenski et al, 1994). Other clinical laboratories have observed the c.3468G>A variant in conjunction with other known pathogenic variants in multiple probands with cystic fibrosis, thus supporting its potentially pathogenic role (SCV000227776.1; personal communication with Ambry Genetics). The G to A substitution at nucleotide position 3468 is conserved through mammals and does not change the amino acid at codon 1156; however, it occurs at the last base pair of coding exon 21, adjacent to the splice donor site of intron 21. Variants at these exonic positions can impact mRNA splicing; however, in silico splicing predictors are inconsistent in their predictions as to whether this particular variant alters mRNA splicing.
Ambry Genetics RCV000624739 SCV000742204 likely pathogenic Inborn genetic diseases 2014-06-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: NEGATIVE - No Relevant Alterations Detected (Step 2)
Mendelics RCV000046899 SCV000886300 pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing
Johns Hopkins Genomics,Johns Hopkins University RCV000046899 SCV000992332 pathogenic Cystic fibrosis 2019-03-07 criteria provided, single submitter clinical testing

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