Submissions for variant NM_004360.5(CDH1):c.48+1G>C

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003513076	SCV004264029	pathogenic	Hereditary diffuse gastric adenocarcinoma	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 1 of the CDH1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with breast cancer, diffuse gastric cancer, invasive lobular breast cancer, and/or signet cell carcinoma (PMID: 20719348, 24366306, 30745422, 35264596). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc.	RCV003513076	SCV005407202	pathogenic	Hereditary diffuse gastric adenocarcinoma	2024-08-27	criteria provided, single submitter	clinical testing	This variant is considered 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. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 20719348, 38873722, 30745422, 29025585].