TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28425	85498;85499;85500	chr2:178560859;178560858;178560857	chr2:179425586;179425585;179425584
N2AB	26784	80575;80576;80577	chr2:178560859;178560858;178560857	chr2:179425586;179425585;179425584
N2A	25857	77794;77795;77796	chr2:178560859;178560858;178560857	chr2:179425586;179425585;179425584
N2B	19360	58303;58304;58305	chr2:178560859;178560858;178560857	chr2:179425586;179425585;179425584
Novex-1	19485	58678;58679;58680	chr2:178560859;178560858;178560857	chr2:179425586;179425585;179425584
Novex-2	19552	58879;58880;58881	chr2:178560859;178560858;178560857	chr2:179425586;179425585;179425584
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-143
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.3269
• 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	None	None	0.012	N	0.258	0.079	0.0806252709748	gnomAD-4.0.0	6.00161E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.56251E-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	0.092	likely_benign	0.0957	benign	-0.698	Destabilizing	0.012	N	0.258	neutral	N	0.460983228	None	None	I
T/C	0.4364	ambiguous	0.4648	ambiguous	-0.34	Destabilizing	0.824	D	0.492	neutral	None	None	None	None	I
T/D	0.6116	likely_pathogenic	0.6151	pathogenic	-0.217	Destabilizing	0.081	N	0.453	neutral	None	None	None	None	I
T/E	0.6173	likely_pathogenic	0.6003	pathogenic	-0.255	Destabilizing	0.081	N	0.462	neutral	None	None	None	None	I
T/F	0.6054	likely_pathogenic	0.5905	pathogenic	-0.955	Destabilizing	0.555	D	0.579	neutral	None	None	None	None	I
T/G	0.133	likely_benign	0.1425	benign	-0.908	Destabilizing	0.035	N	0.415	neutral	None	None	None	None	I
T/H	0.4135	ambiguous	0.416	ambiguous	-1.245	Destabilizing	0.555	D	0.555	neutral	None	None	None	None	I
T/I	0.6712	likely_pathogenic	0.6464	pathogenic	-0.244	Destabilizing	0.117	N	0.509	neutral	N	0.495113759	None	None	I
T/K	0.397	ambiguous	0.374	ambiguous	-0.649	Destabilizing	0.081	N	0.456	neutral	None	None	None	None	I
T/L	0.2936	likely_benign	0.2835	benign	-0.244	Destabilizing	0.149	N	0.463	neutral	None	None	None	None	I
T/M	0.1849	likely_benign	0.1854	benign	0.195	Stabilizing	0.791	D	0.5	neutral	None	None	None	None	I
T/N	0.2057	likely_benign	0.2117	benign	-0.491	Destabilizing	0.062	N	0.361	neutral	D	0.525920141	None	None	I
T/P	0.6112	likely_pathogenic	0.6024	pathogenic	-0.365	Destabilizing	0.117	N	0.493	neutral	N	0.483757453	None	None	I
T/Q	0.4078	ambiguous	0.3994	ambiguous	-0.749	Destabilizing	0.38	N	0.515	neutral	None	None	None	None	I
T/R	0.2725	likely_benign	0.2621	benign	-0.345	Destabilizing	0.38	N	0.514	neutral	None	None	None	None	I
T/S	0.0771	likely_benign	0.0816	benign	-0.751	Destabilizing	None	N	0.108	neutral	N	0.392950082	None	None	I
T/V	0.4833	ambiguous	0.4658	ambiguous	-0.365	Destabilizing	0.149	N	0.356	neutral	None	None	None	None	I
T/W	0.8336	likely_pathogenic	0.8399	pathogenic	-0.886	Destabilizing	0.935	D	0.578	neutral	None	None	None	None	I
T/Y	0.4988	ambiguous	0.5092	ambiguous	-0.65	Destabilizing	0.555	D	0.576	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.