TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18688	56287;56288;56289	chr2:178599839;178599838;178599837	chr2:179464566;179464565;179464564
N2AB	17047	51364;51365;51366	chr2:178599839;178599838;178599837	chr2:179464566;179464565;179464564
N2A	16120	48583;48584;48585	chr2:178599839;178599838;178599837	chr2:179464566;179464565;179464564
N2B	9623	29092;29093;29094	chr2:178599839;178599838;178599837	chr2:179464566;179464565;179464564
Novex-1	9748	29467;29468;29469	chr2:178599839;178599838;178599837	chr2:179464566;179464565;179464564
Novex-2	9815	29668;29669;29670	chr2:178599839;178599838;178599837	chr2:179464566;179464565;179464564
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-116
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4711
• 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
I/V	None	None	0.993	N	0.218	0.291	0.417716871343	gnomAD-4.0.0	2.09355E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.72843E-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
I/A	0.8267	likely_pathogenic	0.7658	pathogenic	-1.745	Destabilizing	0.999	D	0.458	neutral	None	None	None	None	N
I/C	0.9382	likely_pathogenic	0.9138	pathogenic	-1.092	Destabilizing	1.0	D	0.573	neutral	None	None	None	None	N
I/D	0.9988	likely_pathogenic	0.9979	pathogenic	-1.239	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
I/E	0.996	likely_pathogenic	0.9937	pathogenic	-1.204	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
I/F	0.6222	likely_pathogenic	0.5231	ambiguous	-1.165	Destabilizing	1.0	D	0.561	neutral	N	0.486021951	None	None	N
I/G	0.9884	likely_pathogenic	0.9804	pathogenic	-2.109	Highly Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
I/H	0.9968	likely_pathogenic	0.994	pathogenic	-1.428	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
I/K	0.994	likely_pathogenic	0.9905	pathogenic	-1.255	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
I/L	0.2716	likely_benign	0.2377	benign	-0.801	Destabilizing	0.993	D	0.242	neutral	N	0.521279539	None	None	N
I/M	0.2699	likely_benign	0.2269	benign	-0.666	Destabilizing	1.0	D	0.557	neutral	N	0.48652893	None	None	N
I/N	0.9882	likely_pathogenic	0.981	pathogenic	-1.098	Destabilizing	1.0	D	0.646	neutral	N	0.48703591	None	None	N
I/P	0.9905	likely_pathogenic	0.9822	pathogenic	-1.085	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
I/Q	0.9936	likely_pathogenic	0.9905	pathogenic	-1.221	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
I/R	0.9902	likely_pathogenic	0.9851	pathogenic	-0.747	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
I/S	0.9605	likely_pathogenic	0.9342	pathogenic	-1.722	Destabilizing	1.0	D	0.593	neutral	N	0.486275441	None	None	N
I/T	0.823	likely_pathogenic	0.7397	pathogenic	-1.566	Destabilizing	1.0	D	0.545	neutral	N	0.486021951	None	None	N
I/V	0.0961	likely_benign	0.0859	benign	-1.085	Destabilizing	0.993	D	0.218	neutral	N	0.521452897	None	None	N
I/W	0.992	likely_pathogenic	0.9844	pathogenic	-1.294	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
I/Y	0.9787	likely_pathogenic	0.9651	pathogenic	-1.054	Destabilizing	1.0	D	0.558	neutral	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.