FIGC rare germline variants validated by Sanger sequencing
| Proband ID (age diagnosis) | Germline variant | Frequency* (patients, n) | ClinVar (variation ID) | MSI status | ||||
| Gene | cDNA | Type/Location | Variation ID (dbSNP) | FIGC (n=50) | TSI (n=107) | |||
| P1 (59) | PMS1 | c.224C>T | Missense | rs61756360 | 1 | 0 | NR | MSS† |
| P13 (72) | MUTYH | c.36+75C>A | 5’UTR | rs3219467 | 1 | 1 | NR | MSS |
| P15 (75) | PRR5 | c.271C>T | Missense | rs201344303 | 1 | 0 | NR | MSI-H |
| P18 (66) | ATM | c.4306C>T | Missense | rs544891616 | 1 | 1 | VUS (187606) | MSI-H |
| P20 (71) | MUTYH | c.1216C>A | Missense | rs144079536 | 1 | 0 | VUS (41752) | MSS |
| P23 (74) | PRR5 | c.-11+8170G>A | 5’UTR | rs552907174 | 1 | 0 | NR | MSS† |
| P27 (64) | SMAD4 | c.424+5G>A | Intronic | rs200772603 | 1 | 0 | VUS (127950) | MSS† |
| PRSS1 | c.201–99G>C | Intronic | rs530207004 | 1 | 1 | NR | ||
| P30 (71) | MLH1 | c.-202C>T | 5’UTR | rs561267247 | 1 | 0 | NR | MSS† |
| P33 (78) | MSR1 | c.881G>A | Missense | rs41440349 | 1 | 0 | NR | MSI-H |
| P49 (67) | MAP3K6 | c.3711+131G>A | 3’UTR | rs554613210 | 1 | 0 | NR | MSI-H |
| P51‡ (70) | MSR1 | c.482C>A | Missense | rs76147566 | 1 | 1 | NR | MSS† |
*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.