ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1320+1G>C

dbSNP: rs886039685
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328317 SCV001437611 likely pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-24 reviewed by expert panel curation The c.1320+1G>C variant occurs at the canonical splice donor site of exon 9 (PVS1_strong, PM5_supporting). This variant is absent from populations in gnomAD (PM2_supporting; http://gnomad.broadinstitute.org). Splicing analysis in vitro has shown that the C allele results in skipping of exon 9, producing an abnormal in-frame transcript (PS3_supporting; PMID: 8033105, 28301459). Furthermore, this variant has been observed in at least one family meeting IGCLC criteria for HDGC (PS4_supporting; SCV000322628.7). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): PVS1_strong, PM2_supporting, PS3_supporting, PS4_supporting, PM5_supporting.
GeneDx RCV000255500 SCV000322628 pathogenic not provided 2017-05-15 criteria provided, single submitter clinical testing This variant is denoted CDH1 c.1320+1G>C or IVS9+1G>C and consists of a G>C nucleotide substitution at the +1 position of intron 9 of the CDH1 gene. This variant destroys a canonical splice donor site and has been shown to result in in-frame skipping of exon 9 (Becker 1994). Even though this variant results in an in-frame transcript, this single exon deletion would result in the loss of 61 residues, which are located within the cadherin 3 domain (UniProt). Based on the currently available information, we consider CDH1 c.1320+1G>C to be pathogenic.
Myriad Genetics, Inc. RCV003335297 SCV004045202 likely pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-28 criteria provided, single submitter clinical testing This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.
OMIM RCV000505772 SCV000599984 pathogenic Blepharocheilodontic syndrome 1 2017-09-20 no assertion criteria provided literature only

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