TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26880	80863;80864;80865	chr2:178565494;178565493;178565492	chr2:179430221;179430220;179430219
N2AB	25239	75940;75941;75942	chr2:178565494;178565493;178565492	chr2:179430221;179430220;179430219
N2A	24312	73159;73160;73161	chr2:178565494;178565493;178565492	chr2:179430221;179430220;179430219
N2B	17815	53668;53669;53670	chr2:178565494;178565493;178565492	chr2:179430221;179430220;179430219
Novex-1	17940	54043;54044;54045	chr2:178565494;178565493;178565492	chr2:179430221;179430220;179430219
Novex-2	18007	54244;54245;54246	chr2:178565494;178565493;178565492	chr2:179430221;179430220;179430219
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-139
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2439
• 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
P/S	None	None	1.0	D	0.767	0.805	0.662503200617	gnomAD-4.0.0	1.59212E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-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	0.7937	likely_pathogenic	0.7715	pathogenic	-1.382	Destabilizing	1.0	D	0.694	prob.neutral	D	0.632103532	None	None	N
P/C	0.9867	likely_pathogenic	0.9863	pathogenic	-1.247	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
P/D	0.998	likely_pathogenic	0.9984	pathogenic	-1.769	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
P/E	0.9958	likely_pathogenic	0.9968	pathogenic	-1.807	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
P/F	0.999	likely_pathogenic	0.999	pathogenic	-1.392	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/G	0.9804	likely_pathogenic	0.9779	pathogenic	-1.628	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
P/H	0.9953	likely_pathogenic	0.9961	pathogenic	-1.1	Destabilizing	1.0	D	0.723	prob.delet.	D	0.648728306	None	None	N
P/I	0.9837	likely_pathogenic	0.9854	pathogenic	-0.814	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/K	0.9974	likely_pathogenic	0.998	pathogenic	-1.003	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
P/L	0.9444	likely_pathogenic	0.9428	pathogenic	-0.814	Destabilizing	1.0	D	0.748	deleterious	D	0.648526501	None	None	N
P/M	0.9925	likely_pathogenic	0.9929	pathogenic	-0.686	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
P/N	0.9958	likely_pathogenic	0.9967	pathogenic	-0.897	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/Q	0.9932	likely_pathogenic	0.9945	pathogenic	-1.2	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
P/R	0.9924	likely_pathogenic	0.9934	pathogenic	-0.456	Destabilizing	1.0	D	0.751	deleterious	D	0.648728306	None	None	N
P/S	0.9713	likely_pathogenic	0.9746	pathogenic	-1.337	Destabilizing	1.0	D	0.767	deleterious	D	0.622786585	None	None	N
P/T	0.9602	likely_pathogenic	0.9679	pathogenic	-1.278	Destabilizing	1.0	D	0.757	deleterious	D	0.648526501	None	None	N
P/V	0.9482	likely_pathogenic	0.9507	pathogenic	-0.971	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9997	pathogenic	-1.498	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
P/Y	0.9986	likely_pathogenic	0.9988	pathogenic	-1.17	Destabilizing	1.0	D	0.751	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.