TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17278	52057;52058;52059	chr2:178609478;178609477;178609476	chr2:179474205;179474204;179474203
N2AB	15637	47134;47135;47136	chr2:178609478;178609477;178609476	chr2:179474205;179474204;179474203
N2A	14710	44353;44354;44355	chr2:178609478;178609477;178609476	chr2:179474205;179474204;179474203
N2B	8213	24862;24863;24864	chr2:178609478;178609477;178609476	chr2:179474205;179474204;179474203
Novex-1	8338	25237;25238;25239	chr2:178609478;178609477;178609476	chr2:179474205;179474204;179474203
Novex-2	8405	25438;25439;25440	chr2:178609478;178609477;178609476	chr2:179474205;179474204;179474203
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-112
• Domain position: 28
• Structural Position: 45
• Q(SASA): 0.4755
• 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
T/I	None	None	0.966	D	0.613	0.289	0.475272412942	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93751E-06	0	0
T/S	None	None	0.051	D	0.171	0.106	0.243972157842	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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
T/A	0.0758	likely_benign	0.0632	benign	-0.533	Destabilizing	0.454	N	0.351	neutral	D	0.532192752	None	None	I
T/C	0.3327	likely_benign	0.3107	benign	-0.445	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	I
T/D	0.3328	likely_benign	0.3005	benign	0.105	Stabilizing	0.728	D	0.469	neutral	None	None	None	None	I
T/E	0.211	likely_benign	0.1882	benign	0.091	Stabilizing	0.016	N	0.236	neutral	None	None	None	None	I
T/F	0.2363	likely_benign	0.234	benign	-0.725	Destabilizing	0.991	D	0.612	neutral	None	None	None	None	I
T/G	0.2238	likely_benign	0.1968	benign	-0.756	Destabilizing	0.728	D	0.521	neutral	None	None	None	None	I
T/H	0.1874	likely_benign	0.1742	benign	-0.976	Destabilizing	0.974	D	0.593	neutral	None	None	None	None	I
T/I	0.1372	likely_benign	0.1276	benign	-0.044	Destabilizing	0.966	D	0.613	neutral	D	0.536926569	None	None	I
T/K	0.1184	likely_benign	0.1036	benign	-0.581	Destabilizing	0.728	D	0.463	neutral	None	None	None	None	I
T/L	0.0959	likely_benign	0.0922	benign	-0.044	Destabilizing	0.842	D	0.475	neutral	None	None	None	None	I
T/M	0.1045	likely_benign	0.0956	benign	-0.025	Destabilizing	0.991	D	0.557	neutral	None	None	None	None	I
T/N	0.1132	likely_benign	0.1075	benign	-0.502	Destabilizing	0.801	D	0.414	neutral	D	0.536406494	None	None	I
T/P	0.4771	ambiguous	0.4047	ambiguous	-0.175	Destabilizing	0.966	D	0.577	neutral	N	0.513573635	None	None	I
T/Q	0.1635	likely_benign	0.1366	benign	-0.61	Destabilizing	0.172	N	0.248	neutral	None	None	None	None	I
T/R	0.1119	likely_benign	0.1	benign	-0.36	Destabilizing	0.842	D	0.513	neutral	None	None	None	None	I
T/S	0.098	likely_benign	0.09	benign	-0.747	Destabilizing	0.051	N	0.171	neutral	D	0.529765736	None	None	I
T/V	0.1052	likely_benign	0.0968	benign	-0.175	Destabilizing	0.842	D	0.431	neutral	None	None	None	None	I
T/W	0.6148	likely_pathogenic	0.5876	pathogenic	-0.729	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	I
T/Y	0.2719	likely_benign	0.251	benign	-0.463	Destabilizing	0.991	D	0.614	neutral	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.