TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34970	105133;105134;105135	chr2:178531707;178531706;178531705	chr2:179396434;179396433;179396432
N2AB	33329	100210;100211;100212	chr2:178531707;178531706;178531705	chr2:179396434;179396433;179396432
N2A	32402	97429;97430;97431	chr2:178531707;178531706;178531705	chr2:179396434;179396433;179396432
N2B	25905	77938;77939;77940	chr2:178531707;178531706;178531705	chr2:179396434;179396433;179396432
Novex-1	26030	78313;78314;78315	chr2:178531707;178531706;178531705	chr2:179396434;179396433;179396432
Novex-2	26097	78514;78515;78516	chr2:178531707;178531706;178531705	chr2:179396434;179396433;179396432
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-163
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.4029
• 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	None	None	0.061	N	0.131	0.119	0.16115917748	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/I	None	None	0.988	N	0.457	0.302	0.478376075226	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/S	None	None	0.704	N	0.431	0.132	0.207176502487	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0774	likely_benign	0.1195	benign	-0.256	Destabilizing	0.061	N	0.131	neutral	N	0.46046594	None	None	N
T/C	0.6804	likely_pathogenic	0.8141	pathogenic	-0.229	Destabilizing	0.999	D	0.473	neutral	None	None	None	None	N
T/D	0.4439	ambiguous	0.6432	pathogenic	0.03	Stabilizing	0.884	D	0.419	neutral	None	None	None	None	N
T/E	0.3123	likely_benign	0.5011	ambiguous	-0.063	Destabilizing	0.079	N	0.198	neutral	None	None	None	None	N
T/F	0.3817	ambiguous	0.6218	pathogenic	-0.847	Destabilizing	0.997	D	0.55	neutral	None	None	None	None	N
T/G	0.33	likely_benign	0.4348	ambiguous	-0.346	Destabilizing	0.939	D	0.497	neutral	None	None	None	None	N
T/H	0.3816	ambiguous	0.5833	pathogenic	-0.64	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
T/I	0.2333	likely_benign	0.5056	ambiguous	-0.142	Destabilizing	0.988	D	0.457	neutral	N	0.495253304	None	None	N
T/K	0.3005	likely_benign	0.5175	ambiguous	-0.324	Destabilizing	0.939	D	0.441	neutral	None	None	None	None	N
T/L	0.1288	likely_benign	0.2428	benign	-0.142	Destabilizing	0.939	D	0.437	neutral	None	None	None	None	N
T/M	0.1073	likely_benign	0.1763	benign	0.017	Stabilizing	0.999	D	0.451	neutral	None	None	None	None	N
T/N	0.1756	likely_benign	0.3086	benign	-0.083	Destabilizing	0.959	D	0.397	neutral	N	0.521861116	None	None	N
T/P	0.1662	likely_benign	0.2673	benign	-0.153	Destabilizing	0.988	D	0.452	neutral	N	0.464140964	None	None	N
T/Q	0.2723	likely_benign	0.4627	ambiguous	-0.334	Destabilizing	0.982	D	0.448	neutral	None	None	None	None	N
T/R	0.2582	likely_benign	0.4639	ambiguous	-0.045	Destabilizing	0.982	D	0.448	neutral	None	None	None	None	N
T/S	0.127	likely_benign	0.215	benign	-0.251	Destabilizing	0.704	D	0.431	neutral	N	0.490268772	None	None	N
T/V	0.1518	likely_benign	0.2921	benign	-0.153	Destabilizing	0.939	D	0.367	neutral	None	None	None	None	N
T/W	0.7825	likely_pathogenic	0.9003	pathogenic	-0.887	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
T/Y	0.4709	ambiguous	0.6727	pathogenic	-0.587	Destabilizing	0.997	D	0.553	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.