PGPC-43 | BRCA1‡ (NM_007300.3) | c.68_69delAG, p.(Glu23Valfs*17), het | Breast and ovarian cancer, AD | Pathogenic: PVS1, PS3, PS4, PP5 (20) | FHx of prostate cancer (70–80 yr) | 1, 2, 3 |
PGPC-16† | ELN (NM_001278914.1) | c.455–1G > A, p.?, het | Supravalvular aortic stenosis, AD | Likely pathogenic: PVS1, PM2 (21) | No relevant PHx/FHx, normal heart CT | 1, 2, 3 |
PGPC-25† | LMNA§ (NM_170707.3) | c.1748C > T, p.(Ser583Leu), het | Lipodystrophy, familial partial, AD/AR | Likely pathogenic: PM1, PM2, PP1, PP3 (22) | PHx of hypercholesterolemia, hyperpigmented patch | 1, 2, 3 |
PGPC-16† | LZTR1 (NM_006767.3) | c.774delT, p.(Phe258Leufs*93), het | Schwannomatosis, AD | Likely pathogenic: PVS1, PM2 (23) | No relevant PHx/FHx | 1, 2, 3 |
PGPC-40† | SLC7A9 (NM_001243036.1) | c.614dupA, p.(Asn206Glufs*3), het | Cystinuria, AD/AR | Pathogenic: PVS1, PS4-M, PP5 (24), (25) | No relevant PHx/FHx | 1, 2, 3 |
PGPC-27† | Multiple | Seq[GRCh37] Xp22.33q28(1_155270560)x1[0.7] | Mosaic Turner syndrome | Pathogenic (26) | No obvious clinical manifestation | 1, 2 |
PGPC-02, PGPC-27† | CHEK2 (NM_145862.2) | c.470T > C, p.(Ile157Thr), het | Cancer susceptibility, AD/AR | Risk factor: PS4, PP5 (27), (28) | 27: FHx of breast, prostate, throat cancer | 1, 2, 3 |
PGPC-25,† PGPC-29 | F2 (NM_000506.3) | c.*97G > A (20210G > A), het | Thrombophilia, AD/AR | Risk factor: PS3, PS4 (29) | 29: No relevant PHx/FHx | 1, 2, 3 |
PGPC-24 | LPL (NM_000237.2) | c.953A > G, p.(Asn318Ser), het | Dyslipidemia, AD/AR | Risk factor: PS3, PS4 (30)– (32) | PHx/FHx of hypercholesterolemia, FHx of CAD (60 yr) | 1, 2, 3 |
PGPC-36 | MUTYH¶ (NM_001048171.1) | c.892–2A > G, p.?, het | Familial adenomatous polyposis, AR; colorectal cancer risk, AD | Risk factor (AD), pathogenic (AR): PVS1, PS3, PP5, BS1 (33), (34) | FHx of gastric cancer (70–80 yr) | 1, 2, 3 |
PGPC-48 | PCDH15 (NM_001142769.1) | chr10:g. [55741501_57660800del], het (1.9 Mb) | Neuropsychiatric disease risk, AD; deafness/Usher syndrome, AR | Risk factor (AD), likely pathogenic (AR): PVS1, PM2 (35)– (38) | FHx of ADHD | 1, 3 |
Variants of uncertain significance |
PGPC-40† | ANK2 (NM_001148.4) | c.4373A > G, p.(Glu1458Gly), het | Long QT syndrome, cardiac arrhythmia, AD | VUS: PS3, PP1, BS1 (39)– (41)** | No relevant PHx/FHx | 1, 2 |
PGPC-40† | CDH1 (NM_004360.3) | c.2343A > T, p.(Glu781Asp), het | CDH1-related cancer, AD | VUS: PM2 (42), (43) | FHx of gastric cancer (75–80 yr) | 1, 2 |
PGPC-19 | CHMP2B (NM_014043.3) | c.85A > G, p.(Ile29Val), het | Amyotrophic lateral sclerosis, Frontotemporal dementia, AD | VUS: PS3, PP5, BP4 (44)– (46) | No relevant PHx/FHx | 1 |
PGPC-14 | KCNE2 (NM_172201.1) | c.29C > T, p.(Thr10Met), het | Long QT syndrome, Atrial fibrillation, AD | VUS: PP5, BS1 (47), (48) | ND | 1, 2 |
Uncertain significance, genetic counselling recommended |
PGPC-32 | MT-TV | m.1659T > C, 7% heteroplasmy | Childhood neurologic disorder | Likely pathogenic†† (49) | ND | 1, 4 |
PGPC-22 | Multiple | Seq[GRCh37] inv(20) (q11.23q13.12), chr20:g. [35583655_44214109inv], het (8.6 Mb) | Likely minimal risk for unbalanced aberrations in family members | Large, rare structural variant | ND | 1 |
53 of 56 PGPC participants | 172 recessive carrier variants (e.g., 5 pathogenic CFTR alleles) | Multiple | Potential disease risk in family members | Risk factor | ND | 1, 4 |
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