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The association between ITGB1BP2 and dilated cardiomyopathy (MONDO_0005021) is currently classified as Limited. In a case report, a missense variant, c.938C>G (p.Ala313Gly), was identified in a 45-year-old male with familial dilated cardiomyopathy, suggesting a possible role for ITGB1BP2 in disease pathogenesis (PMID:23124043). In a larger multi‐patient study screening 928 individuals, only a very low number of ITGB1BP2 variations were detected among hypertensive and cardiopathic patients, and no clear genotype/phenotype correlation was established (PMID:20017903).
Functional assessment studies have not provided definitive evidence that the identified variants disrupt melusin function in a way that contributes to the development of dilated cardiomyopathy. Despite the biological plausibility of melusin in myocardial stress signaling, the experimental data remain inconclusive. Key take‑home sentence: While ITGB1BP2 is a candidate gene for dilated cardiomyopathy, further genetic and functional studies are needed before it can be reliably used in diagnostic or commercial applications.
Gene–Disease AssociationLimitedOnly one familial case with the missense variant c.938C>G (p.Ala313Gly) was identified (PMID:23124043), supported by a larger cohort study showing an extremely low number of variants without a clear phenotype correlation (PMID:20017903). Genetic EvidenceLimitedGenetic evidence is restricted to a single candidate missense mutation among 255 patients and a few additional rare variants from a cohort study, none of which have demonstrated robust segregation. Functional EvidenceLimitedFunctional studies have not confirmed a clear mechanistic effect of ITGB1BP2 variants on heart muscle function, leaving the pathogenicity unresolved. |