TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34366	103321;103322;103323	chr2:178533519;178533518;178533517	chr2:179398246;179398245;179398244
N2AB	32725	98398;98399;98400	chr2:178533519;178533518;178533517	chr2:179398246;179398245;179398244
N2A	31798	95617;95618;95619	chr2:178533519;178533518;178533517	chr2:179398246;179398245;179398244
N2B	25301	76126;76127;76128	chr2:178533519;178533518;178533517	chr2:179398246;179398245;179398244
Novex-1	25426	76501;76502;76503	chr2:178533519;178533518;178533517	chr2:179398246;179398245;179398244
Novex-2	25493	76702;76703;76704	chr2:178533519;178533518;178533517	chr2:179398246;179398245;179398244
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-162
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4668
• 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
K/E	None	None	0.999	N	0.585	0.525	0.421550847248	gnomAD-4.0.0	1.59167E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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
K/A	0.986	likely_pathogenic	0.9838	pathogenic	-0.307	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	I
K/C	0.9821	likely_pathogenic	0.9816	pathogenic	-0.402	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
K/D	0.9957	likely_pathogenic	0.9943	pathogenic	0.114	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
K/E	0.9699	likely_pathogenic	0.9516	pathogenic	0.183	Stabilizing	0.999	D	0.585	neutral	N	0.457756496	None	None	I
K/F	0.9957	likely_pathogenic	0.9951	pathogenic	-0.127	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
K/G	0.9858	likely_pathogenic	0.9815	pathogenic	-0.619	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
K/H	0.8757	likely_pathogenic	0.8545	pathogenic	-0.884	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
K/I	0.975	likely_pathogenic	0.9709	pathogenic	0.472	Stabilizing	1.0	D	0.723	prob.delet.	N	0.442901687	None	None	I
K/L	0.9484	likely_pathogenic	0.941	pathogenic	0.472	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	I
K/M	0.9572	likely_pathogenic	0.9424	pathogenic	0.261	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	I
K/N	0.9886	likely_pathogenic	0.9843	pathogenic	-0.152	Destabilizing	1.0	D	0.705	prob.neutral	N	0.515823365	None	None	I
K/P	0.9907	likely_pathogenic	0.9881	pathogenic	0.243	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
K/Q	0.7921	likely_pathogenic	0.7319	pathogenic	-0.267	Destabilizing	1.0	D	0.683	prob.neutral	N	0.480998715	None	None	I
K/R	0.1838	likely_benign	0.1648	benign	-0.381	Destabilizing	0.999	D	0.545	neutral	N	0.453177395	None	None	I
K/S	0.9857	likely_pathogenic	0.9814	pathogenic	-0.771	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
K/T	0.9418	likely_pathogenic	0.9215	pathogenic	-0.515	Destabilizing	1.0	D	0.683	prob.neutral	N	0.438706588	None	None	I
K/V	0.9683	likely_pathogenic	0.9649	pathogenic	0.243	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
K/W	0.9904	likely_pathogenic	0.9874	pathogenic	-0.031	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
K/Y	0.9813	likely_pathogenic	0.9799	pathogenic	0.259	Stabilizing	1.0	D	0.699	prob.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.