Genetic profile plays an important role in the presentation and progression of HCM. This retrospective study provides the largest genetic analysis of Swedish HCM patients and highlights clear differences between genotype-positive (G⁺) and genotype-negative (G⁻) groups. Published in Scientific Reports, it explored genotype–phenotype associations in 225 unrelated index patients from 2010 to 2021.

Among the 172 patients who completed genetic testing, 38% were G⁺ for pathogenic or likely pathogenic variants. Most variants involved MYBPC3 and MYH7, the two sarcomeric genes most strongly linked to HCM. Another 43% were G⁻, and 19% carried variants of uncertain significance (VUS), which were excluded from comparative analyses.

G⁺ patients were younger (p = 0.010), had a higher prevalence of family history of HCM (p < 0.001), and showed greater maximum LV wall thickness (p = 0.03). They also had a higher incidence of SCD (p = 0.045) compared with G⁻ patients. At the first clinical assessment, HCM was diagnosed in 43% of G⁺ families versus 2.7% of G⁻ families (p < 0.001).

Despite the absence of a detectable mutation, G⁻ patients did not have complete protection from adverse outcomes, highlighting the need for thorough clinical evaluation in all individuals with suspected HCM.
These findings support the value of genetic testing in improving risk stratification, guiding family screening, and informing earlier management decisions in hypertrophic cardiomyopathy.