Pathogenic and likely pathogenic germline variants in patients with mCRPC
| Gene | Transcript | Variant | Protein effect | PROMOTE classification | Pathogenic in ClinVar | Disease causing in HGMD | Phenotype |
|---|---|---|---|---|---|---|---|
| ATM | NM_000051.3 | c.7271T>G; p.Val2424Gly | Missense | Pathogenic | Yes | Yes | Ataxia telangiectasia |
| ATM | NM_000051.3 | c.3245_3247delinsTGAT; p.His1082LeufsX14 | Frameshift | Pathogenic | Yes | Yes | Ataxia telangiectasia |
| ATR | NM_001184.3 | c.4957C>T; p.Arg1653X | Stop gained | Likely pathogenic | Familial cutaneous telangiectasia and cancer syndrome | ||
| BRCA2 | NM_000059.3 | c.469_470delAA; p.Lys157ValfsX25 | Frameshift | Likely pathogenic | Yes | Yes | Hereditary breast/ovarian cancer syndrome |
| BRCA2 | NM_000059.3 | c.6444dupT; p.Ile2149TyrfsX2 | Frameshift | Pathogenic | Yes | Yes | Hereditary breast/ovarian cancer syndrome |
| BRCA2 | NM_000059.3 | c.9513_9516delACTT; p.Leu3172AlafsX44 | Frameshift | Pathogenic | Yes | Hereditary breast/ovarian cancer syndrome | |
| FANCL | NM_001114636.1 | c.1111_1114dupATTA; p.Thr372AsnfsX13 | Frameshift | Likely pathogenic | Yes | Fanconi anaemia | |
| MSR1 | NM_138715.2 | c.183delT; p.Phe61LeufsX10 | Frameshift | Likely pathogenic | Hereditary prostate cancer | ||
| MUTYH | NM_001128425.1 | c.1187G>A; p.Gly396Asp | Missense | Pathogenic | Yes | Yes | MUTYH-associated polyposis |
| RB1 | NM_000321.2 | c.1960+1G>C | Splice donor | Likely pathogenic | retinoblastoma | ||
| TSHR | NM_000369.2 | c.1349G>A; p.Arg450His | Missense | Pathogenic | Yes | Thyroid carcinoma | |
| WRN | NM_000553.4 | c.525delG; p.Trp175X | Frameshift | Likely pathogenic | Werner syndrome |
Bolded genes are associated with increased prostate cancer risk.
HGMD, Human Gene Mutation Database; mCRPC, metastatic castrate-resistant prostate cancer; PROMOTE, Prostate Cancer Medically Optimized Genome-Enhanced Therapy.