Table 2

FIGC rare germline variants validated by Sanger sequencing

Proband ID (age diagnosis)Germline variantFrequency* (patients, n)ClinVar (variation ID)MSI status
GenecDNAType/LocationVariation ID (dbSNP)FIGC (n=50)TSI (n=107)
P1 (59) PMS1 c.224C>TMissensers6175636010NRMSS†
P13 (72) MUTYH c.36+75C>A5’UTRrs321946711NRMSS
P15 (75) PRR5 c.271C>TMissensers20134430310NRMSI-H
P18 (66) ATM c.4306C>TMissensers54489161611VUS (187606)MSI-H
P20 (71) MUTYH c.1216C>AMissensers14407953610VUS (41752)MSS
P23 (74) PRR5 c.-11+8170G>A5’UTRrs55290717410NRMSS†
P27 (64) SMAD4 c.424+5G>AIntronicrs20077260310VUS (127950)MSS†
PRSS1 c.201–99G>CIntronicrs53020700411NR
P30 (71) MLH1 c.-202C>T5’UTRrs56126724710NRMSS†
P33 (78) MSR1 c.881G>AMissensers4144034910NRMSI-H
P49 (67) MAP3K6 c.3711+131G>A3’UTRrs55461321010NRMSI-H
P51‡ (70) MSR1 c.482C>AMissensers7614756611NRMSS†
  • *Not detected in any individual from HDGC, SIGC cohorts, and from the selected European populations from the 1000 Genomes Project.

  • †Tumours were classified as stable, despite presenting low MSI.

  • ‡Probands also had colon cancer.

  • dbSNP, single nucleotide polymorphism database; FIGC, familial intestinal gastric cancer; HDGC, hereditary diffuse gastric cancer; ID, identification; MSI, microsatellite instable; MSI-H, microsatellite instable high; MSS, microsatellite stable; NR, not reported in ClinVar; SIGC, sporadic intestinal gastric cancer; TSI, normal Tuscany population (1000 Genomes Project); UTR, untranslated ; VUS, variants of uncertain significance.