TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17037	51334;51335;51336	chr2:178611020;178611019;178611018	chr2:179475747;179475746;179475745
N2AB	15396	46411;46412;46413	chr2:178611020;178611019;178611018	chr2:179475747;179475746;179475745
N2A	14469	43630;43631;43632	chr2:178611020;178611019;178611018	chr2:179475747;179475746;179475745
N2B	7972	24139;24140;24141	chr2:178611020;178611019;178611018	chr2:179475747;179475746;179475745
Novex-1	8097	24514;24515;24516	chr2:178611020;178611019;178611018	chr2:179475747;179475746;179475745
Novex-2	8164	24715;24716;24717	chr2:178611020;178611019;178611018	chr2:179475747;179475746;179475745
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-111
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.4554
• Predicted PPI site: N

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/K	None	None	0.994	N	0.709	0.394	0.484400871567	gnomAD-4.0.0	1.594E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43513E-05	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	0.0838	likely_benign	0.0896	benign	-0.474	Destabilizing	0.9	D	0.455	neutral	N	0.513674547	None	None	N
T/C	0.5246	ambiguous	0.5576	ambiguous	-0.319	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
T/D	0.4246	ambiguous	0.476	ambiguous	0.299	Stabilizing	0.995	D	0.703	prob.neutral	None	None	None	None	N
T/E	0.2947	likely_benign	0.3128	benign	0.236	Stabilizing	0.995	D	0.709	prob.delet.	None	None	None	None	N
T/F	0.3278	likely_benign	0.383	ambiguous	-0.926	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
T/G	0.298	likely_benign	0.3153	benign	-0.621	Destabilizing	0.983	D	0.588	neutral	None	None	None	None	N
T/H	0.2939	likely_benign	0.3099	benign	-0.936	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/I	0.2131	likely_benign	0.2493	benign	-0.202	Destabilizing	0.997	D	0.747	deleterious	D	0.542148152	None	None	N
T/K	0.1733	likely_benign	0.1872	benign	-0.351	Destabilizing	0.994	D	0.709	prob.delet.	N	0.515083035	None	None	N
T/L	0.1554	likely_benign	0.1738	benign	-0.202	Destabilizing	0.992	D	0.59	neutral	None	None	None	None	N
T/M	0.1145	likely_benign	0.1183	benign	-0.028	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
T/N	0.1506	likely_benign	0.1694	benign	-0.164	Destabilizing	0.995	D	0.593	neutral	None	None	None	None	N
T/P	0.3493	ambiguous	0.4003	ambiguous	-0.264	Destabilizing	0.997	D	0.749	deleterious	D	0.550818857	None	None	N
T/Q	0.2187	likely_benign	0.223	benign	-0.374	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
T/R	0.1779	likely_benign	0.1826	benign	-0.121	Destabilizing	0.997	D	0.749	deleterious	N	0.508727303	None	None	N
T/S	0.1076	likely_benign	0.1136	benign	-0.414	Destabilizing	0.63	D	0.267	neutral	N	0.455969967	None	None	N
T/V	0.1551	likely_benign	0.1717	benign	-0.264	Destabilizing	0.992	D	0.479	neutral	None	None	None	None	N
T/W	0.7569	likely_pathogenic	0.7927	pathogenic	-0.903	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/Y	0.4105	ambiguous	0.4644	ambiguous	-0.622	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N

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.