TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28007	84244;84245;84246	chr2:178562113;178562112;178562111	chr2:179426840;179426839;179426838
N2AB	26366	79321;79322;79323	chr2:178562113;178562112;178562111	chr2:179426840;179426839;179426838
N2A	25439	76540;76541;76542	chr2:178562113;178562112;178562111	chr2:179426840;179426839;179426838
N2B	18942	57049;57050;57051	chr2:178562113;178562112;178562111	chr2:179426840;179426839;179426838
Novex-1	19067	57424;57425;57426	chr2:178562113;178562112;178562111	chr2:179426840;179426839;179426838
Novex-2	19134	57625;57626;57627	chr2:178562113;178562112;178562111	chr2:179426840;179426839;179426838
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-142
• Domain position: 45
• Structural Position: 109
• Q(SASA): 0.9246
• 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/I	None	None	0.994	N	0.513	0.455	0.341934017632	gnomAD-4.0.0	3.18518E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85982E-06	0	3.02645E-05

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	0.1046	likely_benign	0.1384	benign	-0.122	Destabilizing	0.958	D	0.443	neutral	N	0.489742257	None	None	N
T/C	0.7141	likely_pathogenic	0.8266	pathogenic	-0.311	Destabilizing	1.0	D	0.551	neutral	None	None	None	None	N
T/D	0.5679	likely_pathogenic	0.72	pathogenic	-0.018	Destabilizing	0.995	D	0.497	neutral	None	None	None	None	N
T/E	0.4614	ambiguous	0.6112	pathogenic	-0.109	Destabilizing	0.991	D	0.498	neutral	None	None	None	None	N
T/F	0.5318	ambiguous	0.6434	pathogenic	-0.787	Destabilizing	0.998	D	0.533	neutral	None	None	None	None	N
T/G	0.3002	likely_benign	0.406	ambiguous	-0.183	Destabilizing	0.991	D	0.441	neutral	None	None	None	None	N
T/H	0.4928	ambiguous	0.6311	pathogenic	-0.345	Destabilizing	1.0	D	0.537	neutral	None	None	None	None	N
T/I	0.4072	ambiguous	0.5155	ambiguous	-0.084	Destabilizing	0.994	D	0.513	neutral	N	0.481189429	None	None	N
T/K	0.39	ambiguous	0.5054	ambiguous	-0.265	Destabilizing	0.991	D	0.501	neutral	None	None	None	None	N
T/L	0.1555	likely_benign	0.2038	benign	-0.084	Destabilizing	0.968	D	0.473	neutral	None	None	None	None	N
T/M	0.1309	likely_benign	0.1565	benign	-0.129	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	N
T/N	0.2145	likely_benign	0.314	benign	-0.039	Destabilizing	0.994	D	0.57	neutral	N	0.486240592	None	None	N
T/P	0.1418	likely_benign	0.2486	benign	-0.072	Destabilizing	0.067	N	0.365	neutral	N	0.491107694	None	None	N
T/Q	0.3303	likely_benign	0.4394	ambiguous	-0.246	Destabilizing	0.995	D	0.537	neutral	None	None	None	None	N
T/R	0.3425	ambiguous	0.4621	ambiguous	0.026	Stabilizing	0.995	D	0.517	neutral	None	None	None	None	N
T/S	0.1331	likely_benign	0.1789	benign	-0.193	Destabilizing	0.958	D	0.441	neutral	N	0.437889285	None	None	N
T/V	0.2589	likely_benign	0.3295	benign	-0.072	Destabilizing	0.984	D	0.479	neutral	None	None	None	None	N
T/W	0.8196	likely_pathogenic	0.8872	pathogenic	-0.888	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
T/Y	0.5649	likely_pathogenic	0.6807	pathogenic	-0.559	Destabilizing	0.998	D	0.53	neutral	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.