TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29870	89833;89834;89835	chr2:178553292;178553291;178553290	chr2:179418019;179418018;179418017
N2AB	28229	84910;84911;84912	chr2:178553292;178553291;178553290	chr2:179418019;179418018;179418017
N2A	27302	82129;82130;82131	chr2:178553292;178553291;178553290	chr2:179418019;179418018;179418017
N2B	20805	62638;62639;62640	chr2:178553292;178553291;178553290	chr2:179418019;179418018;179418017
Novex-1	20930	63013;63014;63015	chr2:178553292;178553291;178553290	chr2:179418019;179418018;179418017
Novex-2	20997	63214;63215;63216	chr2:178553292;178553291;178553290	chr2:179418019;179418018;179418017
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-147
• Domain position: 29
• Structural Position: 45
• Q(SASA): 0.4104
• 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/A	rs372796632	-0.565	0.454	N	0.39	0.208	None	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/A	rs372796632	-0.565	0.454	N	0.39	0.208	None	gnomAD-4.0.0	6.86391E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99475E-07	0	0
T/P	None	None	0.966	D	0.524	0.585	0.557713733399	gnomAD-4.0.0	6.86391E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	0	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	0.0693	likely_benign	0.0676	benign	-0.561	Destabilizing	0.454	N	0.39	neutral	N	0.503101997	None	None	N
T/C	0.34	ambiguous	0.3549	ambiguous	-0.525	Destabilizing	0.998	D	0.546	neutral	None	None	None	None	N
T/D	0.3571	ambiguous	0.333	benign	0.082	Stabilizing	0.728	D	0.434	neutral	None	None	None	None	N
T/E	0.2419	likely_benign	0.224	benign	0.073	Stabilizing	0.842	D	0.426	neutral	None	None	None	None	N
T/F	0.2246	likely_benign	0.2139	benign	-0.808	Destabilizing	0.991	D	0.645	neutral	None	None	None	None	N
T/G	0.237	likely_benign	0.2317	benign	-0.78	Destabilizing	0.525	D	0.469	neutral	None	None	None	None	N
T/H	0.2003	likely_benign	0.194	benign	-0.986	Destabilizing	0.974	D	0.643	neutral	None	None	None	None	N
T/I	0.122	likely_benign	0.1122	benign	-0.084	Destabilizing	0.966	D	0.531	neutral	D	0.522381191	None	None	N
T/K	0.149	likely_benign	0.1427	benign	-0.527	Destabilizing	0.842	D	0.424	neutral	None	None	None	None	N
T/L	0.0818	likely_benign	0.0796	benign	-0.084	Destabilizing	0.842	D	0.427	neutral	None	None	None	None	N
T/M	0.0891	likely_benign	0.0857	benign	-0.116	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	N
T/N	0.0992	likely_benign	0.0971	benign	-0.517	Destabilizing	0.022	N	0.154	neutral	N	0.475531393	None	None	N
T/P	0.4287	ambiguous	0.3987	ambiguous	-0.211	Destabilizing	0.966	D	0.524	neutral	D	0.525423693	None	None	N
T/Q	0.1741	likely_benign	0.1726	benign	-0.61	Destabilizing	0.974	D	0.541	neutral	None	None	None	None	N
T/R	0.1382	likely_benign	0.134	benign	-0.315	Destabilizing	0.949	D	0.513	neutral	None	None	None	None	N
T/S	0.096	likely_benign	0.0952	benign	-0.753	Destabilizing	0.051	N	0.193	neutral	N	0.461887305	None	None	N
T/V	0.0945	likely_benign	0.0911	benign	-0.211	Destabilizing	0.842	D	0.376	neutral	None	None	None	None	N
T/W	0.6003	likely_pathogenic	0.5795	pathogenic	-0.813	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
T/Y	0.2456	likely_benign	0.2381	benign	-0.528	Destabilizing	0.991	D	0.646	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.