TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27469	82630;82631;82632	chr2:178563727;178563726;178563725	chr2:179428454;179428453;179428452
N2AB	25828	77707;77708;77709	chr2:178563727;178563726;178563725	chr2:179428454;179428453;179428452
N2A	24901	74926;74927;74928	chr2:178563727;178563726;178563725	chr2:179428454;179428453;179428452
N2B	18404	55435;55436;55437	chr2:178563727;178563726;178563725	chr2:179428454;179428453;179428452
Novex-1	18529	55810;55811;55812	chr2:178563727;178563726;178563725	chr2:179428454;179428453;179428452
Novex-2	18596	56011;56012;56013	chr2:178563727;178563726;178563725	chr2:179428454;179428453;179428452
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-88
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.6278
• 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
P/A	rs769678793	0.065	0.011	N	0.321	0.199	0.223146558224	gnomAD-2.1.1	6.43E-05	None	None	None	None	I	None	0	0	None	0	9.24499E-04	None	0	None	0	0	0
P/A	rs769678793	0.065	0.011	N	0.321	0.199	0.223146558224	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	3.86997E-04	None	0	0	0	0	4.78011E-04
P/A	rs769678793	0.065	0.011	N	0.321	0.199	0.223146558224	gnomAD-4.0.0	9.91514E-06	None	None	None	None	I	None	0	0	None	0	2.6775E-04	None	0	0	2.54292E-06	0	1.60056E-05
P/R	None	None	None	N	0.219	0.091	0.149567049428	gnomAD-4.0.0	1.59127E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85824E-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
P/A	0.0868	likely_benign	0.0824	benign	-0.403	Destabilizing	0.011	N	0.321	neutral	N	0.469261509	None	None	I
P/C	0.313	likely_benign	0.322	benign	-0.55	Destabilizing	0.747	D	0.387	neutral	None	None	None	None	I
P/D	0.7103	likely_pathogenic	0.6978	pathogenic	-0.106	Destabilizing	0.035	N	0.56	neutral	None	None	None	None	I
P/E	0.3681	ambiguous	0.3704	ambiguous	-0.231	Destabilizing	0.018	N	0.402	neutral	None	None	None	None	I
P/F	0.45	ambiguous	0.4585	ambiguous	-0.806	Destabilizing	0.06	N	0.551	neutral	None	None	None	None	I
P/G	0.4181	ambiguous	0.4104	ambiguous	-0.506	Destabilizing	0.035	N	0.496	neutral	None	None	None	None	I
P/H	0.2141	likely_benign	0.2104	benign	-0.149	Destabilizing	0.204	N	0.427	neutral	None	None	None	None	I
P/I	0.1389	likely_benign	0.1326	benign	-0.291	Destabilizing	None	N	0.2	neutral	None	None	None	None	I
P/K	0.1807	likely_benign	0.1866	benign	-0.108	Destabilizing	None	N	0.221	neutral	None	None	None	None	I
P/L	0.0701	likely_benign	0.0777	benign	-0.291	Destabilizing	None	N	0.125	neutral	N	0.473493087	None	None	I
P/M	0.195	likely_benign	0.1973	benign	-0.191	Destabilizing	0.06	N	0.499	neutral	None	None	None	None	I
P/N	0.4352	ambiguous	0.4225	ambiguous	0.112	Stabilizing	0.035	N	0.505	neutral	None	None	None	None	I
P/Q	0.1523	likely_benign	0.1499	benign	-0.18	Destabilizing	0.087	N	0.512	neutral	N	0.476569344	None	None	I
P/R	0.1279	likely_benign	0.1351	benign	0.356	Stabilizing	None	N	0.219	neutral	N	0.509819246	None	None	I
P/S	0.1949	likely_benign	0.1802	benign	-0.268	Destabilizing	0.006	N	0.367	neutral	N	0.467922063	None	None	I
P/T	0.1023	likely_benign	0.0983	benign	-0.296	Destabilizing	None	N	0.177	neutral	N	0.458622422	None	None	I
P/V	0.1003	likely_benign	0.098	benign	-0.295	Destabilizing	None	N	0.189	neutral	None	None	None	None	I
P/W	0.6033	likely_pathogenic	0.6294	pathogenic	-0.851	Destabilizing	0.747	D	0.449	neutral	None	None	None	None	I
P/Y	0.4105	ambiguous	0.4199	ambiguous	-0.503	Destabilizing	0.204	N	0.499	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.