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A recent case report (PMID:36820582) described a single family affected by lung adenocarcinoma in which the heterozygous THSD7B variant, c.4000A>G (p.Ser1334Gly), co‑segregated with the disease. The affected family included the proband and 4 additional affected relatives (PMID:36820582), demonstrating minimal but consistent genetic evidence. The identified variant was detected via whole exome sequencing and confirmed by Sanger sequencing, with deleterious predictions by SIFT, PolyPhen2, and MutationTaster. Structural protein analysis further indicated that this substitution likely reduces protein stability by markedly altering minimum free energy values (PMID:36820582).
In parallel, functional assessments provided supportive in‑silico evidence; protein modeling and I‑Mutant2.0 analysis suggested that the mutation adversely impacts THSD7B protein conformation and stability, consistent with its putative role in familial lung adenocarcinoma. Although the evidence is currently limited to a single pedigree, the convergence of segregation data and functional predictions offers clinically meaningful insights that may aid diagnostic decision‑making and targeted genetic counseling.
Gene–Disease AssociationLimitedAssociation supported by a single family with 5 affected individuals (proband plus 4 relatives) harboring the heterozygous THSD7B variant (PMID:36820582). Genetic EvidenceLimitedThe genetic evidence is based on one pedigree where the recurrent c.4000A>G (p.Ser1334Gly) variant segregated with lung adenocarcinoma in affected individuals (PMID:36820582). Functional EvidenceModerateIn‑silico and protein structural analyses, including predictions by SIFT, PolyPhen2, MutationTaster, and I‑Mutant2.0, indicate an adverse impact on protein stability, supporting the variant’s role in disease pathogenesis (PMID:36820582). |