Table 1.
Characteristics of PTEN PHTS variants of unknown significance.
| DNA variant1 | Amino acid substitution1 | Reported in databases2 | Phenotype3 | Age / Sex4 | Reference5 | |||
|---|---|---|---|---|---|---|---|---|
| HGMD | ClinVar | COSMIC | cBioPortal | |||||
| c.77 C > T | p.(Thr26Ile)/T26I | (CM151666) | 3 (189399) | 1, GBM (COSM6936497) | 1, GBM |
Macrocephaly Autism Mental retardation |
11 / M | [50] |
| c.284 C > G | p.(Pro95Arg)/P95R | (CM221495) | - | - | - |
Macrocephaly Polyps, hamartomas |
39 / M | [29] |
| c.529 T > A | p.(Tyr177Asn)/Y177N | (CM221496) | 1 (873327) | - | - |
Macrocephaly Motor delay |
5 / M | [29] |
| c.781 C > G | p.(Gln261Glu)/Q261E | (CM221497) | 1 (873325) | - | - |
Macrocephaly Polyps, lipomas Overgrowth |
34 / M | [29] |
| c.829 A > G | p.(Thr277Ala)/T277A | (CM221498) | 1 (571869) |
1, EC 1, t-all (COSM1349598) |
1, UC |
Macrocephaly Developmental disorder Overgrowth |
9 / M | [29] |
| c.929 A > G | p.(Asp310Gly)/D310G | (CM221499) | 3 (566673) |
2, EC 1, EH 1, LC (COSM1968270) |
1, EC 1, Chol |
Macrocephaly Polyps, hamartomas Several cancers |
29 / M | [29] |
1PTEN DNA germline and protein variants are indicated following HGVS recommended nomenclature. Protein variants are also indicated with the single-letter code amino acid nomenclature. Nucleotide and amino acid numbering corresponds to accessions NM_000314.8 and NP_000305.3, respectively.
2HGMD, Human Gene Mutation Database (Professional) (2022.3); ClinVar (NCBI); COSMIC, Catalogue of Somatic Mutations in Cancer (Wellcome Trust Sanger Institute); cBioPortal, cBioportal for Cancer Genomics (MSK Cancer Center). In the case of HGMD, ClinVar, and COSMIC databases, the ID of the variants is indicated in brackets. Numbers indicate the number of cases with the mutation, followed by the tumor type (GBM glioblastoma, EC endometrium carcinoma, t-all T cell acute lymphoblastic leukemia, EH endometrium hyperplasia, LC liver carcinoma, UC uterine carcinosarcoma, Chol cholangiocarcinoma). All analyzed variants are found with relatively low frequency in patients and in tumors. Note that HGMD database only provides 1 submitted case by variant. - no cases annotated in the database.
3See reference [29] for a more detailed phenotype of each PTEN variant carrier patient.
4Age is indicated in years; M male.
5Original references (to the best of our knowledge) for description of germline DNA variants and patients are provided.