TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17251	51976;51977;51978	chr2:178609559;178609558;178609557	chr2:179474286;179474285;179474284
N2AB	15610	47053;47054;47055	chr2:178609559;178609558;178609557	chr2:179474286;179474285;179474284
N2A	14683	44272;44273;44274	chr2:178609559;178609558;178609557	chr2:179474286;179474285;179474284
N2B	8186	24781;24782;24783	chr2:178609559;178609558;178609557	chr2:179474286;179474285;179474284
Novex-1	8311	25156;25157;25158	chr2:178609559;178609558;178609557	chr2:179474286;179474285;179474284
Novex-2	8378	25357;25358;25359	chr2:178609559;178609558;178609557	chr2:179474286;179474285;179474284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-112
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6584
• Predicted PPI site: I

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/I	rs1304051107	-0.788	0.016	N	0.301	0.068	0.416833835346	gnomAD-2.1.1	4.13E-06	None	None	None	None	I	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
V/I	rs1304051107	-0.788	0.016	N	0.301	0.068	0.416833835346	gnomAD-4.0.0	2.06186E-06	None	None	None	None	I	None	0	4.51182E-05	None	0	0	None	0	0	9.02377E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.7566	likely_pathogenic	0.7653	pathogenic	-1.161	Destabilizing	0.834	D	0.597	neutral	N	0.502328418	None	None	I
V/C	0.9584	likely_pathogenic	0.9525	pathogenic	-0.904	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	I
V/D	0.9944	likely_pathogenic	0.9936	pathogenic	-0.556	Destabilizing	0.973	D	0.717	prob.delet.	N	0.503888643	None	None	I
V/E	0.9875	likely_pathogenic	0.9851	pathogenic	-0.533	Destabilizing	0.979	D	0.681	prob.neutral	None	None	None	None	I
V/F	0.8763	likely_pathogenic	0.8433	pathogenic	-0.779	Destabilizing	0.946	D	0.723	prob.delet.	N	0.503541927	None	None	I
V/G	0.8206	likely_pathogenic	0.8233	pathogenic	-1.493	Destabilizing	0.973	D	0.713	prob.delet.	N	0.503888643	None	None	I
V/H	0.9975	likely_pathogenic	0.9967	pathogenic	-1.076	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	I
V/I	0.1331	likely_benign	0.1344	benign	-0.356	Destabilizing	0.016	N	0.301	neutral	N	0.500768193	None	None	I
V/K	0.9939	likely_pathogenic	0.9918	pathogenic	-0.888	Destabilizing	0.979	D	0.677	prob.neutral	None	None	None	None	I
V/L	0.7214	likely_pathogenic	0.7039	pathogenic	-0.356	Destabilizing	0.263	N	0.531	neutral	N	0.501808343	None	None	I
V/M	0.7671	likely_pathogenic	0.7634	pathogenic	-0.429	Destabilizing	0.959	D	0.724	prob.delet.	None	None	None	None	I
V/N	0.9853	likely_pathogenic	0.9838	pathogenic	-0.733	Destabilizing	0.993	D	0.716	prob.delet.	None	None	None	None	I
V/P	0.9861	likely_pathogenic	0.9786	pathogenic	-0.588	Destabilizing	0.993	D	0.692	prob.neutral	None	None	None	None	I
V/Q	0.9922	likely_pathogenic	0.9906	pathogenic	-0.813	Destabilizing	0.993	D	0.685	prob.neutral	None	None	None	None	I
V/R	0.9898	likely_pathogenic	0.9866	pathogenic	-0.562	Destabilizing	0.979	D	0.715	prob.delet.	None	None	None	None	I
V/S	0.9498	likely_pathogenic	0.9488	pathogenic	-1.326	Destabilizing	0.979	D	0.693	prob.neutral	None	None	None	None	I
V/T	0.8835	likely_pathogenic	0.8875	pathogenic	-1.18	Destabilizing	0.87	D	0.711	prob.delet.	None	None	None	None	I
V/W	0.998	likely_pathogenic	0.997	pathogenic	-0.983	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	I
V/Y	0.9853	likely_pathogenic	0.979	pathogenic	-0.645	Destabilizing	0.979	D	0.733	prob.delet.	None	None	None	None	I

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.