ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.3067_3072del (p.Ile1023_Val1024del) (rs121908767)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000046775 SCV000074788 pathogenic Cystic fibrosis 2016-07-01 criteria provided, single submitter clinical testing This sequence change deletes 6 nucleotides from exon 19 of the CFTR mRNA (c.3067_3072del). This leads to the deletion of 2 amino acid residues in the CFTR protein (p.Ile1023_Val1024del) but otherwise preserves the integrity of the reading frame. The frequency data for this variant (rs397508492) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has been reported with a pathogenic variant in several individuals with cystic fibrosis (PMID: 7516234, 12394343, 22627569, 15287992) or congenital absence of the vas deferens (PMID: 22020151). In four of these individuals this variant was confirmed to be in trans with the pathogenic variant (PMID: 7516234, 15287992). In the literature, this variant is also known as 3199del6 or 3195del6. ClinVar contains an entry for this variant (Variation ID: 38480). An experimental study did not detect a CFTR transcript in an affected individual who carried both this c.3067_3072del variant and a truncating variant on the opposite allele (PMID: 8707304). However, a CFTR transcript was detected in the parent who only carried the c.3067_3072del variant, raising concerns about the validity of this experimental analysis. No functional investigation into the effect of this variant on protein function has been reported. In summary, this is a rare in-frame deletion that has been observed in trans with two different pathogenic variants in multiple affected individuals, and in combination with pathogenic variants (phase unknown) in several others. For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000757083 SCV000331277 pathogenic not provided 2012-08-06 criteria provided, single submitter clinical testing
Counsyl RCV000046775 SCV000678118 pathogenic Cystic fibrosis 2015-04-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000046775 SCV000696944 pathogenic Cystic fibrosis 2016-01-18 criteria provided, single submitter clinical testing Variant summary: The c.3067_3072delATAGTG (a.k.a. 3199del6) in CFTR gene is an in-frame deletion that expected to remove Ile1023 and Val1024 from the CFTR protein. Mutation Taster predicts deleterious outcome. The variant is absent from the large and broad cohorts of the ExAC project. The variant of interest has been identified in multiple affected individuals presented with CF and was referred as causative mutation in peer-reviewed publications. At least one reputable clinical laboratory/diagnostic center classified the variant as Pathogenic. Taking together, the variant was classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757083 SCV000885187 pathogenic not provided 2017-05-18 criteria provided, single submitter clinical testing
Mendelics RCV000046775 SCV000886159 likely pathogenic Cystic fibrosis 2018-11-05 criteria provided, single submitter clinical testing

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