How clinical health-risk findings are derived

The health-risk analyser screens 89 clinically significant genes against a curated subset of ClinVar plus expert annotation from Haeckel's clinical genetics review board. The panel covers cardiovascular conditions (LDLR, APOB, PCSK9, MYH7, MYBPC3, KCNQ1, KCNH2), hereditary cancer syndromes (BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, APC, MUTYH, TP53, PTEN, RB1, VHL), metabolic conditions (HFE, ATP7B, SERPINA1, HNF1A, HNF4A, GCK), and selected neurological and pharmacogenomic-adjacent genes.

ClinVar matching

Each variant typed in your file is looked up in ClinVar by chromosome and position. When a match exists, the ClinVar classification (pathogenic, likely pathogenic, VUS, likely benign, benign) is applied. When the same position carries multiple submissions with conflicting classifications, the analyser uses the ClinVar review status (one to four stars) to prefer expert-panel-reviewed classifications over single-submitter ones, and reports the conflict if it cannot be resolved.

Sex-aware X-linked handling

X-linked recessive conditions affect biological males (XY) and biological females (XX) very differently. A pathogenic variant in an X-linked recessive gene is fully expressed in XY because there is no second X to compensate, but is usually carrier-only in XX where the wild-type allele on the other X provides function. The analyser uses the user's genotype-inferred biological sex (not self-reported) to apply the correct inheritance model and report the correct phenotype risk.

Cases where the genotype-inferred sex disagrees with self-reported sex are flagged for the user to resolve, since the disagreement is sometimes a clerical error and sometimes a true clinical signal (intersex variation, mosaic sex chromosomes).

Penetrance and age-stratified risk

A pathogenic variant does not guarantee disease. Each of the 89 genes carries a penetrance curve, derived from large cohort studies, that gives the cumulative probability of developing the associated phenotype by age 30, 50, 70, and across lifetime. BRCA1 carriers, for example, face a roughly 60-70% lifetime risk of breast cancer compared with the population baseline of about 12%, with most of the excess risk concentrated between ages 30 and 60. The platform reports the carrier-specific curve and the population baseline side by side so the user can see both.

Actionability tags

• Surveillance: extra screening (BRCA1 → annual breast MRI starting age 25-30, MLH1 → colonoscopy every 1-2 years starting age 20).
• Preventive surgery: prophylactic mastectomy, oophorectomy, or colectomy considered for selected high-penetrance conditions.
• Intervention: pharmacological intervention shown to reduce risk (statins for FH, tamoxifen for high-risk breast cancer carriers).
• None: no validated intervention exists; the finding is informational only.