TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2719	8380;8381;8382	chr2:178770637;178770636;178770635	chr2:179635364;179635363;179635362
N2AB	2719	8380;8381;8382	chr2:178770637;178770636;178770635	chr2:179635364;179635363;179635362
N2A	2719	8380;8381;8382	chr2:178770637;178770636;178770635	chr2:179635364;179635363;179635362
N2B	2673	8242;8243;8244	chr2:178770637;178770636;178770635	chr2:179635364;179635363;179635362
Novex-1	2673	8242;8243;8244	chr2:178770637;178770636;178770635	chr2:179635364;179635363;179635362
Novex-2	2673	8242;8243;8244	chr2:178770637;178770636;178770635	chr2:179635364;179635363;179635362
Novex-3	2719	8380;8381;8382	chr2:178770637;178770636;178770635	chr2:179635364;179635363;179635362

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-17
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.476
• 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/A	rs2091324218	None	0.998	D	0.559	0.262	0.308904156042	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92382E-04	None	0	0	0	0	0
T/A	rs2091324218	None	0.998	D	0.559	0.262	0.308904156042	gnomAD-4.0.0	2.56179E-06	None	None	None	None	I	None	0	0	None	0	2.42436E-05	None	0	0	2.39175E-06	0	0
T/S	None	None	0.999	D	0.581	0.266	0.27479166964	gnomAD-4.0.0	1.59114E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85656E-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	0.1396	likely_benign	0.1783	benign	-0.268	Destabilizing	0.998	D	0.559	neutral	D	0.530411215	None	None	I
T/C	0.6857	likely_pathogenic	0.749	pathogenic	-0.197	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	I
T/D	0.8152	likely_pathogenic	0.8447	pathogenic	0.001	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	I
T/E	0.625	likely_pathogenic	0.6677	pathogenic	-0.088	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	I
T/F	0.6324	likely_pathogenic	0.6864	pathogenic	-0.795	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
T/G	0.5458	ambiguous	0.5959	pathogenic	-0.378	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
T/H	0.6789	likely_pathogenic	0.7154	pathogenic	-0.64	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
T/I	0.3223	likely_benign	0.4147	ambiguous	-0.1	Destabilizing	0.884	D	0.415	neutral	D	0.563749935	None	None	I
T/K	0.4205	ambiguous	0.4452	ambiguous	-0.368	Destabilizing	1.0	D	0.608	neutral	N	0.506390802	None	None	I
T/L	0.1538	likely_benign	0.1898	benign	-0.1	Destabilizing	0.994	D	0.551	neutral	None	None	None	None	I
T/M	0.1127	likely_benign	0.1291	benign	0.058	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	I
T/N	0.354	ambiguous	0.4245	ambiguous	-0.085	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	I
T/P	0.2438	likely_benign	0.2793	benign	-0.129	Destabilizing	1.0	D	0.588	neutral	D	0.534996171	None	None	I
T/Q	0.4636	ambiguous	0.499	ambiguous	-0.346	Destabilizing	1.0	D	0.601	neutral	None	None	None	None	I
T/R	0.3864	ambiguous	0.4002	ambiguous	-0.048	Destabilizing	1.0	D	0.589	neutral	N	0.500273899	None	None	I
T/S	0.2621	likely_benign	0.3071	benign	-0.267	Destabilizing	0.999	D	0.581	neutral	D	0.553918992	None	None	I
T/V	0.232	likely_benign	0.2866	benign	-0.129	Destabilizing	0.985	D	0.566	neutral	None	None	None	None	I
T/W	0.8887	likely_pathogenic	0.8958	pathogenic	-0.825	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
T/Y	0.7226	likely_pathogenic	0.7673	pathogenic	-0.539	Destabilizing	1.0	D	0.697	prob.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.