Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328468 | SCV000864594 | likely pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-30 | reviewed by expert panel | curation | The c.1137G>T p. (Thr379=) variant results in a G to non-G change at the last nucleotide of an exon (PVS1_Moderate). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant affects the same splice site as a well-characterized splice variant with similar or worse in silico/ RNA predictions (PP3_Moderate). Additionally, this variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 26182300). 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_Moderate, PM2_Supporting, PP3_Moderate, PS4_Supporting. |
Myriad Genetics, |
RCV003336166 | SCV004044980 | likely pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-13 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data]. |