Table 4.

Genetic variant classification, co-segregation analysis, and clinical interpretation in HAE-nC1-INH patients

Patient #	Gene	cDNA change	Protein change	ACMG classification	Family data summary	Co-segregation observation	Final interpretation
1	MYOF	c.5923G > A	p.Glu1975Lys	VUS (PM2)	No family tested	Not available	Variant of uncertain significance
2	MYOF	c.6001 C > G	p.Arg2001Gly	VUS (PM2)	Daughters negative; mother deceased (symptomatic)	Incomplete	Variant of uncertain significance
3	MYOF	c.3965 C > G	p.Ala1322Gly	VUS (PM2)	Mother carrier, asymptomatic	Yes	Variant of uncertain significance
4	MYOF	c.1097G > T	p.Arg366Leu	VUS (PM2)	Not tested	Not available	Variant of uncertain significance
5	HS3ST6	c.497G > A	p.Arg166His	VUS (PM2)	Mother carrier, asymptomatic	Yes	Variant of uncertain significance
6	FXII	c.303_304del	p.His101Glnfs*36	Likely pathogenic (PVS1 + PM2)	Father carrier (asymptomatic); mother and sister negative	Partial (carrier asymptomatic)	Likely pathogenic
7	KNG1	c.1690 C > T	p.Gln564Ter	Likely pathogenic (PVS1 + PM2)	No family data	Not available	Likely pathogenic
8	KNG1	c.1143G > C	p.Arg381Ser	VUS (PM2)	No family data	Not available	Variant of uncertain significance

ACMG classification was determined based on 2015 ACMG/AMP criteria. “VUS” denotes “variant of uncertain significance.” “Partial” co-segregation indicates that the variant was found in a relative without symptoms (suggesting incomplete penetrance)

Clinical interpretation incorporates genotype, phenotype, family history, and treatment response

Patient numbers correspond to those listed in Table 3 for HAE-nC1-INH