TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25367	76324;76325;76326	chr2:178570033;178570032;178570031	chr2:179434760;179434759;179434758
N2AB	23726	71401;71402;71403	chr2:178570033;178570032;178570031	chr2:179434760;179434759;179434758
N2A	22799	68620;68621;68622	chr2:178570033;178570032;178570031	chr2:179434760;179434759;179434758
N2B	16302	49129;49130;49131	chr2:178570033;178570032;178570031	chr2:179434760;179434759;179434758
Novex-1	16427	49504;49505;49506	chr2:178570033;178570032;178570031	chr2:179434760;179434759;179434758
Novex-2	16494	49705;49706;49707	chr2:178570033;178570032;178570031	chr2:179434760;179434759;179434758
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: Fn3-72
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.563
• 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	rs756655305	-0.082	0.999	N	0.791	0.456	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
T/I	rs756655305	-0.082	0.999	N	0.791	0.456	None	gnomAD-4.0.0	1.11467E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.00191E-05	0	0
T/N	None	None	0.999	N	0.633	0.374	0.46614307118	gnomAD-4.0.0	1.59239E-06	None	None	None	None	N	None	0	0	None	0	2.77901E-05	None	0	0	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	0.1127	likely_benign	0.0978	benign	-0.627	Destabilizing	0.981	D	0.457	neutral	N	0.480918346	None	None	N
T/C	0.472	ambiguous	0.4779	ambiguous	-0.355	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/D	0.7176	likely_pathogenic	0.6191	pathogenic	0.213	Stabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
T/E	0.6762	likely_pathogenic	0.5544	ambiguous	0.154	Stabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
T/F	0.4306	ambiguous	0.3733	ambiguous	-1.014	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/G	0.2398	likely_benign	0.2151	benign	-0.788	Destabilizing	0.997	D	0.655	neutral	None	None	None	None	N
T/H	0.4302	ambiguous	0.3631	ambiguous	-1.045	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
T/I	0.3515	ambiguous	0.2887	benign	-0.311	Destabilizing	0.999	D	0.791	deleterious	N	0.499137959	None	None	N
T/K	0.4629	ambiguous	0.3696	ambiguous	-0.458	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
T/L	0.1561	likely_benign	0.1372	benign	-0.311	Destabilizing	0.998	D	0.652	neutral	None	None	None	None	N
T/M	0.1196	likely_benign	0.1049	benign	-0.033	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/N	0.1693	likely_benign	0.1394	benign	-0.247	Destabilizing	0.999	D	0.633	neutral	N	0.474966863	None	None	N
T/P	0.1426	likely_benign	0.1155	benign	-0.387	Destabilizing	0.999	D	0.789	deleterious	N	0.480411367	None	None	N
T/Q	0.3686	ambiguous	0.2966	benign	-0.484	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
T/R	0.4504	ambiguous	0.3602	ambiguous	-0.17	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/S	0.1213	likely_benign	0.103	benign	-0.538	Destabilizing	0.905	D	0.324	neutral	N	0.484561016	None	None	N
T/V	0.2326	likely_benign	0.2025	benign	-0.387	Destabilizing	0.998	D	0.538	neutral	None	None	None	None	N
T/W	0.7643	likely_pathogenic	0.7339	pathogenic	-0.946	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/Y	0.4902	ambiguous	0.4413	ambiguous	-0.695	Destabilizing	1.0	D	0.795	deleterious	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.