TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24439	73540;73541;73542	chr2:178572817;178572816;178572815	chr2:179437544;179437543;179437542
N2AB	22798	68617;68618;68619	chr2:178572817;178572816;178572815	chr2:179437544;179437543;179437542
N2A	21871	65836;65837;65838	chr2:178572817;178572816;178572815	chr2:179437544;179437543;179437542
N2B	15374	46345;46346;46347	chr2:178572817;178572816;178572815	chr2:179437544;179437543;179437542
Novex-1	15499	46720;46721;46722	chr2:178572817;178572816;178572815	chr2:179437544;179437543;179437542
Novex-2	15566	46921;46922;46923	chr2:178572817;178572816;178572815	chr2:179437544;179437543;179437542
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-132
• Domain position: 9
• Structural Position: 14
• Q(SASA): 0.5362
• 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/I	rs750110781	0.297	0.006	N	0.255	0.118	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	8.92E-06	0
T/I	rs750110781	0.297	0.006	N	0.255	0.118	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs750110781	0.297	0.006	N	0.255	0.118	None	gnomAD-4.0.0	5.12694E-06	None	None	None	None	I	None	5.07683E-05	0	None	0	0	None	0	0	2.3942E-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	0.0905	likely_benign	0.1037	benign	-0.503	Destabilizing	0.139	N	0.273	neutral	N	0.493681727	None	None	I
T/C	0.283	likely_benign	0.3193	benign	-0.428	Destabilizing	0.007	N	0.265	neutral	None	None	None	None	I
T/D	0.5357	ambiguous	0.586	pathogenic	0.306	Stabilizing	0.543	D	0.329	neutral	None	None	None	None	I
T/E	0.525	ambiguous	0.5292	ambiguous	0.308	Stabilizing	0.704	D	0.351	neutral	None	None	None	None	I
T/F	0.2744	likely_benign	0.325	benign	-0.625	Destabilizing	0.893	D	0.377	neutral	None	None	None	None	I
T/G	0.2812	likely_benign	0.3366	benign	-0.742	Destabilizing	0.704	D	0.343	neutral	None	None	None	None	I
T/H	0.2876	likely_benign	0.3399	benign	-0.894	Destabilizing	0.944	D	0.35	neutral	None	None	None	None	I
T/I	0.1207	likely_benign	0.1302	benign	0.03	Stabilizing	0.006	N	0.255	neutral	N	0.49184764	None	None	I
T/K	0.4687	ambiguous	0.4592	ambiguous	-0.445	Destabilizing	0.704	D	0.339	neutral	None	None	None	None	I
T/L	0.1048	likely_benign	0.1159	benign	0.03	Stabilizing	0.329	N	0.379	neutral	None	None	None	None	I
T/M	0.0892	likely_benign	0.0958	benign	-0.025	Destabilizing	0.944	D	0.373	neutral	None	None	None	None	I
T/N	0.0861	likely_benign	0.1074	benign	-0.427	Destabilizing	0.023	N	0.219	neutral	N	0.483150799	None	None	I
T/P	0.2178	likely_benign	0.2581	benign	-0.115	Destabilizing	0.975	D	0.404	neutral	N	0.518929233	None	None	I
T/Q	0.3234	likely_benign	0.3505	ambiguous	-0.505	Destabilizing	0.944	D	0.386	neutral	None	None	None	None	I
T/R	0.4189	ambiguous	0.4211	ambiguous	-0.257	Destabilizing	0.944	D	0.404	neutral	None	None	None	None	I
T/S	0.0996	likely_benign	0.1224	benign	-0.716	Destabilizing	0.065	N	0.224	neutral	N	0.49080749	None	None	I
T/V	0.0982	likely_benign	0.0981	benign	-0.115	Destabilizing	0.031	N	0.175	neutral	None	None	None	None	I
T/W	0.6679	likely_pathogenic	0.7171	pathogenic	-0.624	Destabilizing	0.995	D	0.392	neutral	None	None	None	None	I
T/Y	0.3066	likely_benign	0.3582	ambiguous	-0.346	Destabilizing	0.981	D	0.355	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.