TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28767	86524;86525;86526	chr2:178559833;178559832;178559831	chr2:179424560;179424559;179424558
N2AB	27126	81601;81602;81603	chr2:178559833;178559832;178559831	chr2:179424560;179424559;179424558
N2A	26199	78820;78821;78822	chr2:178559833;178559832;178559831	chr2:179424560;179424559;179424558
N2B	19702	59329;59330;59331	chr2:178559833;178559832;178559831	chr2:179424560;179424559;179424558
Novex-1	19827	59704;59705;59706	chr2:178559833;178559832;178559831	chr2:179424560;179424559;179424558
Novex-2	19894	59905;59906;59907	chr2:178559833;178559832;178559831	chr2:179424560;179424559;179424558
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: Ig-144
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.9081
• 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
K/E	rs1348921301	None	0.958	N	0.669	0.392	0.410071178582	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/E	rs1348921301	None	0.958	N	0.669	0.392	0.410071178582	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-05	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	0.686	likely_pathogenic	0.692	pathogenic	-0.011	Destabilizing	0.968	D	0.677	prob.neutral	None	None	None	None	N
K/C	0.8257	likely_pathogenic	0.8426	pathogenic	-0.358	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/D	0.8878	likely_pathogenic	0.8872	pathogenic	0.017	Stabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	N
K/E	0.4392	ambiguous	0.4478	ambiguous	0.046	Stabilizing	0.958	D	0.669	neutral	N	0.486617836	None	None	N
K/F	0.9249	likely_pathogenic	0.9243	pathogenic	-0.146	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/G	0.787	likely_pathogenic	0.7842	pathogenic	-0.229	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	N
K/H	0.3953	ambiguous	0.3997	ambiguous	-0.417	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
K/I	0.7569	likely_pathogenic	0.7535	pathogenic	0.489	Stabilizing	0.995	D	0.74	deleterious	None	None	None	None	N
K/L	0.6257	likely_pathogenic	0.6323	pathogenic	0.489	Stabilizing	0.991	D	0.649	neutral	None	None	None	None	N
K/M	0.5066	ambiguous	0.519	ambiguous	0.101	Stabilizing	0.999	D	0.693	prob.neutral	N	0.515143798	None	None	N
K/N	0.7533	likely_pathogenic	0.7549	pathogenic	0.011	Stabilizing	0.988	D	0.708	prob.delet.	N	0.487378304	None	None	N
K/P	0.7201	likely_pathogenic	0.7219	pathogenic	0.35	Stabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
K/Q	0.212	likely_benign	0.2165	benign	-0.087	Destabilizing	0.988	D	0.699	prob.neutral	N	0.486110857	None	None	N
K/R	0.08	likely_benign	0.0772	benign	-0.127	Destabilizing	0.142	N	0.397	neutral	N	0.447440715	None	None	N
K/S	0.7558	likely_pathogenic	0.7628	pathogenic	-0.444	Destabilizing	0.968	D	0.692	prob.neutral	None	None	None	None	N
K/T	0.466	ambiguous	0.4683	ambiguous	-0.258	Destabilizing	0.988	D	0.674	neutral	D	0.536406494	None	None	N
K/V	0.6863	likely_pathogenic	0.6841	pathogenic	0.35	Stabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	N
K/W	0.8905	likely_pathogenic	0.8871	pathogenic	-0.192	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/Y	0.8257	likely_pathogenic	0.8234	pathogenic	0.158	Stabilizing	0.998	D	0.725	prob.delet.	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.