TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17169	51730;51731;51732	chr2:178609918;178609917;178609916	chr2:179474645;179474644;179474643
N2AB	15528	46807;46808;46809	chr2:178609918;178609917;178609916	chr2:179474645;179474644;179474643
N2A	14601	44026;44027;44028	chr2:178609918;178609917;178609916	chr2:179474645;179474644;179474643
N2B	8104	24535;24536;24537	chr2:178609918;178609917;178609916	chr2:179474645;179474644;179474643
Novex-1	8229	24910;24911;24912	chr2:178609918;178609917;178609916	chr2:179474645;179474644;179474643
Novex-2	8296	25111;25112;25113	chr2:178609918;178609917;178609916	chr2:179474645;179474644;179474643
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-13
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.2499
• 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/M	rs1167283297	None	1.0	N	0.788	0.512	0.442363741745	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/M	rs1167283297	None	1.0	N	0.788	0.512	0.442363741745	gnomAD-4.0.0	2.56469E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.79148E-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
K/A	0.8557	likely_pathogenic	0.7848	pathogenic	-0.339	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
K/C	0.9241	likely_pathogenic	0.8905	pathogenic	-0.437	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
K/D	0.9142	likely_pathogenic	0.8628	pathogenic	-0.166	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
K/E	0.6456	likely_pathogenic	0.5393	ambiguous	-0.075	Destabilizing	0.999	D	0.562	neutral	N	0.484886303	None	None	I
K/F	0.963	likely_pathogenic	0.9413	pathogenic	-0.087	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
K/G	0.8931	likely_pathogenic	0.8365	pathogenic	-0.665	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
K/H	0.6041	likely_pathogenic	0.54	ambiguous	-0.9	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
K/I	0.7632	likely_pathogenic	0.7148	pathogenic	0.485	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
K/L	0.6995	likely_pathogenic	0.638	pathogenic	0.485	Stabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
K/M	0.5715	likely_pathogenic	0.5032	ambiguous	0.134	Stabilizing	1.0	D	0.788	deleterious	N	0.471777313	None	None	I
K/N	0.7478	likely_pathogenic	0.6681	pathogenic	-0.36	Destabilizing	1.0	D	0.707	prob.neutral	N	0.511035541	None	None	I
K/P	0.9941	likely_pathogenic	0.9888	pathogenic	0.24	Stabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
K/Q	0.3355	likely_benign	0.2767	benign	-0.387	Destabilizing	1.0	D	0.675	prob.neutral	N	0.487523964	None	None	I
K/R	0.1538	likely_benign	0.1379	benign	-0.498	Destabilizing	0.999	D	0.513	neutral	N	0.476365607	None	None	I
K/S	0.85	likely_pathogenic	0.7889	pathogenic	-0.865	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
K/T	0.6294	likely_pathogenic	0.5586	ambiguous	-0.586	Destabilizing	1.0	D	0.781	deleterious	N	0.473111871	None	None	I
K/V	0.7423	likely_pathogenic	0.6965	pathogenic	0.24	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
K/W	0.9612	likely_pathogenic	0.9392	pathogenic	-0.058	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
K/Y	0.885	likely_pathogenic	0.8345	pathogenic	0.222	Stabilizing	1.0	D	0.841	deleterious	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.