Table 3. Genotypic-phenotypic... | American Society of Hematology

Table 3.

Genotypic-phenotypic characterization and in silico predication of novel variants in the index cases with VWD type 2

Family	Nucleotide change, amino acid change	Exon	FVIII:C, IU/dL⁻¹	VWF:Ag, IU/dL⁻¹	VWF activity, IU/dL⁻¹	VWF:CB, IU/dL⁻¹	VWF activity/VWF:Ag ratio	Diagnosis	In silico analysis*
Family	Nucleotide change, amino acid change	Exon	FVIII:C, IU/dL⁻¹	VWF:Ag, IU/dL⁻¹	VWF activity, IU/dL⁻¹	VWF:CB, IU/dL⁻¹	VWF activity/VWF:Ag ratio	Diagnosis	PolyPhen	SIFT	CADD	M-CAP	PROVEAN	VarSome
I	c.2678T>G, p.Leu893Arg	20	28	30	29	27	0.96	2N; compound with p.R854Q in trans	1	0	31	0.435	−5.78	VUS
II	c.3377G>A, p.Cys1126Tyr	25	40	19	10	10	0.52	2A(IIE)	0.89	0	25.3	0.89	−10.8	VUS
III	c.3425G>T, p.Cys1142Phe	26	71	105	42	34	0.4	2A(IIE)	1	0	27.3	0.18	−10.54	VUS
IV	c.3842T>G, p.Leu1281Arg	28	26	14	6	9	0.42	2A(IIE)	1	0	27.5	0.75	−2.08	Likely pathogenic
V	c.4277G>C, p.Arg1426Phe	28	64	39	12	31	0.31	2M	0.81	0	23.6	0.72	−1.35	Likely pathogenic
VI	c.4970T>C, p.Leu1657Phe	28	51	35	8	2	0.22	2A(IIA)	1	0	24.7	0.84	−2.82	Likely pathogenic
VII	c.5192C>T, p.Ser1731Leu	30	74	67	41	12	0.61	2MCB	0.78	0	28.4	0.67	−3.2	Likely pathogenic
VIII	c.7670G>A, p.Cys2557Tyr	45	58	21	10	7	0.47	2B NY: compound with p.S1263S-P1266L in trans	1	0	24.2	0.22	−4.94	VUS

Family	Nucleotide change, amino acid change	Exon	FVIII:C, IU/dL⁻¹	VWF:Ag, IU/dL⁻¹	VWF activity, IU/dL⁻¹	VWF:CB, IU/dL⁻¹	VWF activity/VWF:Ag ratio	Diagnosis	In silico analysis*
Family	Nucleotide change, amino acid change	Exon	FVIII:C, IU/dL⁻¹	VWF:Ag, IU/dL⁻¹	VWF activity, IU/dL⁻¹	VWF:CB, IU/dL⁻¹	VWF activity/VWF:Ag ratio	Diagnosis	PolyPhen	SIFT	CADD	M-CAP	PROVEAN	VarSome
I	c.2678T>G, p.Leu893Arg	20	28	30	29	27	0.96	2N; compound with p.R854Q in trans	1	0	31	0.435	−5.78	VUS
II	c.3377G>A, p.Cys1126Tyr	25	40	19	10	10	0.52	2A(IIE)	0.89	0	25.3	0.89	−10.8	VUS
III	c.3425G>T, p.Cys1142Phe	26	71	105	42	34	0.4	2A(IIE)	1	0	27.3	0.18	−10.54	VUS
IV	c.3842T>G, p.Leu1281Arg	28	26	14	6	9	0.42	2A(IIE)	1	0	27.5	0.75	−2.08	Likely pathogenic
V	c.4277G>C, p.Arg1426Phe	28	64	39	12	31	0.31	2M	0.81	0	23.6	0.72	−1.35	Likely pathogenic
VI	c.4970T>C, p.Leu1657Phe	28	51	35	8	2	0.22	2A(IIA)	1	0	24.7	0.84	−2.82	Likely pathogenic
VII	c.5192C>T, p.Ser1731Leu	30	74	67	41	12	0.61	2MCB	0.78	0	28.4	0.67	−3.2	Likely pathogenic
VIII	c.7670G>A, p.Cys2557Tyr	45	58	21	10	7	0.47	2B NY: compound with p.S1263S-P1266L in trans	1	0	24.2	0.22	−4.94	VUS

VUS, variant of uncertain (or unknown) significance.

Polyphen score: >0.908, probably damaging; >0.446 and ≤0.908, possibly damaging; ≤0.446, benign. SIFT score: <0.05, deleterious; ≥0.05, tolerated. CADD score: >20, deleterious. M-CAP: >0.025, pathogenic. PROVEAN: ≤−2.5, deleterious; >−2.5, neutral.

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