TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25615	77068;77069;77070	chr2:178569289;178569288;178569287	chr2:179434016;179434015;179434014
N2AB	23974	72145;72146;72147	chr2:178569289;178569288;178569287	chr2:179434016;179434015;179434014
N2A	23047	69364;69365;69366	chr2:178569289;178569288;178569287	chr2:179434016;179434015;179434014
N2B	16550	49873;49874;49875	chr2:178569289;178569288;178569287	chr2:179434016;179434015;179434014
Novex-1	16675	50248;50249;50250	chr2:178569289;178569288;178569287	chr2:179434016;179434015;179434014
Novex-2	16742	50449;50450;50451	chr2:178569289;178569288;178569287	chr2:179434016;179434015;179434014
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: Fn3-74
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.545
• 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/R	rs1707237309	None	0.996	N	0.567	0.234	0.280181792013	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/R	rs1707237309	None	0.996	N	0.567	0.234	0.280181792013	gnomAD-4.0.0	2.57242E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.8058E-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	0.4717	ambiguous	0.523	ambiguous	-0.146	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
K/C	0.7987	likely_pathogenic	0.8354	pathogenic	-0.216	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.8338	likely_pathogenic	0.8648	pathogenic	-0.023	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/E	0.4051	ambiguous	0.4379	ambiguous	-0.015	Destabilizing	0.997	D	0.636	neutral	N	0.466009506	None	None	N
K/F	0.9384	likely_pathogenic	0.9592	pathogenic	-0.356	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/G	0.5726	likely_pathogenic	0.6322	pathogenic	-0.374	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/H	0.4942	ambiguous	0.5558	ambiguous	-0.764	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
K/I	0.709	likely_pathogenic	0.7536	pathogenic	0.381	Stabilizing	0.992	D	0.677	prob.neutral	N	0.518706564	None	None	N
K/L	0.6347	likely_pathogenic	0.7063	pathogenic	0.381	Stabilizing	0.994	D	0.643	neutral	None	None	None	None	N
K/M	0.4974	ambiguous	0.5582	ambiguous	0.411	Stabilizing	1.0	D	0.591	neutral	None	None	None	None	N
K/N	0.6755	likely_pathogenic	0.7269	pathogenic	0.185	Stabilizing	1.0	D	0.726	prob.delet.	N	0.478824296	None	None	N
K/P	0.7737	likely_pathogenic	0.8317	pathogenic	0.234	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/Q	0.2415	likely_benign	0.2707	benign	-0.091	Destabilizing	0.998	D	0.722	prob.delet.	N	0.473254889	None	None	N
K/R	0.0699	likely_benign	0.0747	benign	-0.04	Destabilizing	0.996	D	0.567	neutral	N	0.472189152	None	None	N
K/S	0.5995	likely_pathogenic	0.6545	pathogenic	-0.382	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
K/T	0.3881	ambiguous	0.4579	ambiguous	-0.218	Destabilizing	0.999	D	0.668	neutral	N	0.479620764	None	None	N
K/V	0.5899	likely_pathogenic	0.6459	pathogenic	0.234	Stabilizing	0.995	D	0.661	neutral	None	None	None	None	N
K/W	0.887	likely_pathogenic	0.9219	pathogenic	-0.279	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
K/Y	0.8482	likely_pathogenic	0.8906	pathogenic	0.076	Stabilizing	0.999	D	0.657	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.