TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5349	16270;16271;16272	chr2:178733248;178733247;178733246	chr2:179597975;179597974;179597973
N2AB	5032	15319;15320;15321	chr2:178733248;178733247;178733246	chr2:179597975;179597974;179597973
N2A	4105	12538;12539;12540	chr2:178733248;178733247;178733246	chr2:179597975;179597974;179597973
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-36
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3701
• 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/A	rs2080869632	None	0.9	D	0.539	0.344	0.36036328697	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
T/A	rs2080869632	None	0.9	D	0.539	0.344	0.36036328697	gnomAD-4.0.0	1.25084E-06	None	None	None	None	I	None	0	1.69285E-05	None	0	0	None	0	0	8.52979E-07	0	0
T/I	None	None	0.997	N	0.645	0.42	0.600985507913	gnomAD-4.0.0	1.63129E-06	None	None	None	None	I	None	5.75573E-05	0	None	0	0	None	0	0	0	0	0
T/S	None	None	0.63	N	0.347	0.308	0.296329037015	gnomAD-4.0.0	6.91229E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.05525E-07	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	0.1081	likely_benign	0.0922	benign	-1.068	Destabilizing	0.9	D	0.539	neutral	D	0.526074857	None	None	I
T/C	0.5494	ambiguous	0.5031	ambiguous	-0.623	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
T/D	0.4431	ambiguous	0.3939	ambiguous	0.211	Stabilizing	0.967	D	0.574	neutral	None	None	None	None	I
T/E	0.3179	likely_benign	0.3013	benign	0.283	Stabilizing	0.983	D	0.573	neutral	None	None	None	None	I
T/F	0.2889	likely_benign	0.2547	benign	-0.957	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
T/G	0.4274	ambiguous	0.3674	ambiguous	-1.375	Destabilizing	0.983	D	0.613	neutral	None	None	None	None	I
T/H	0.2356	likely_benign	0.2121	benign	-1.413	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
T/I	0.1958	likely_benign	0.1652	benign	-0.314	Destabilizing	0.997	D	0.645	neutral	N	0.498832327	None	None	I
T/K	0.2181	likely_benign	0.1985	benign	-0.328	Destabilizing	0.983	D	0.583	neutral	None	None	None	None	I
T/L	0.1208	likely_benign	0.107	benign	-0.314	Destabilizing	0.992	D	0.574	neutral	None	None	None	None	I
T/M	0.1028	likely_benign	0.0947	benign	-0.232	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	I
T/N	0.1637	likely_benign	0.1373	benign	-0.439	Destabilizing	0.576	D	0.341	neutral	N	0.518148807	None	None	I
T/P	0.5488	ambiguous	0.449	ambiguous	-0.534	Destabilizing	0.997	D	0.644	neutral	D	0.524805037	None	None	I
T/Q	0.2268	likely_benign	0.2123	benign	-0.491	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	I
T/R	0.1525	likely_benign	0.1372	benign	-0.26	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	I
T/S	0.1327	likely_benign	0.1164	benign	-0.897	Destabilizing	0.63	D	0.347	neutral	N	0.52032232	None	None	I
T/V	0.1535	likely_benign	0.1402	benign	-0.534	Destabilizing	0.992	D	0.542	neutral	None	None	None	None	I
T/W	0.5997	likely_pathogenic	0.5829	pathogenic	-0.825	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
T/Y	0.309	likely_benign	0.2815	benign	-0.571	Destabilizing	0.999	D	0.734	prob.delet.	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.