TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28889	86890;86891;86892	chr2:178559467;178559466;178559465	chr2:179424194;179424193;179424192
N2AB	27248	81967;81968;81969	chr2:178559467;178559466;178559465	chr2:179424194;179424193;179424192
N2A	26321	79186;79187;79188	chr2:178559467;178559466;178559465	chr2:179424194;179424193;179424192
N2B	19824	59695;59696;59697	chr2:178559467;178559466;178559465	chr2:179424194;179424193;179424192
Novex-1	19949	60070;60071;60072	chr2:178559467;178559466;178559465	chr2:179424194;179424193;179424192
Novex-2	20016	60271;60272;60273	chr2:178559467;178559466;178559465	chr2:179424194;179424193;179424192
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: Fn3-98
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.382
• 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/T	None	None	0.967	N	0.425	0.33	0.327419511103	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9227	likely_pathogenic	0.8605	pathogenic	-0.117	Destabilizing	0.916	D	0.368	neutral	None	None	None	None	N
K/C	0.9267	likely_pathogenic	0.8866	pathogenic	-0.33	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
K/D	0.9859	likely_pathogenic	0.9752	pathogenic	0.07	Stabilizing	0.987	D	0.454	neutral	None	None	None	None	N
K/E	0.8673	likely_pathogenic	0.7606	pathogenic	0.094	Stabilizing	0.892	D	0.346	neutral	N	0.460470648	None	None	N
K/F	0.9857	likely_pathogenic	0.9712	pathogenic	-0.176	Destabilizing	0.999	D	0.576	neutral	None	None	None	None	N
K/G	0.8953	likely_pathogenic	0.8311	pathogenic	-0.357	Destabilizing	0.975	D	0.403	neutral	None	None	None	None	N
K/H	0.7152	likely_pathogenic	0.6484	pathogenic	-0.603	Destabilizing	0.997	D	0.457	neutral	None	None	None	None	N
K/I	0.9555	likely_pathogenic	0.9121	pathogenic	0.448	Stabilizing	0.987	D	0.581	neutral	None	None	None	None	N
K/L	0.8544	likely_pathogenic	0.7634	pathogenic	0.448	Stabilizing	0.975	D	0.403	neutral	None	None	None	None	N
K/M	0.7783	likely_pathogenic	0.638	pathogenic	0.236	Stabilizing	0.999	D	0.46	neutral	N	0.511459616	None	None	N
K/N	0.9565	likely_pathogenic	0.9275	pathogenic	0.046	Stabilizing	0.967	D	0.44	neutral	N	0.468226127	None	None	N
K/P	0.9877	likely_pathogenic	0.9811	pathogenic	0.289	Stabilizing	0.996	D	0.418	neutral	None	None	None	None	N
K/Q	0.4312	ambiguous	0.3244	benign	-0.132	Destabilizing	0.967	D	0.455	neutral	N	0.489582834	None	None	N
K/R	0.0819	likely_benign	0.0787	benign	-0.178	Destabilizing	0.025	N	0.27	neutral	N	0.405542872	None	None	N
K/S	0.9408	likely_pathogenic	0.8957	pathogenic	-0.502	Destabilizing	0.916	D	0.368	neutral	None	None	None	None	N
K/T	0.8649	likely_pathogenic	0.76	pathogenic	-0.317	Destabilizing	0.967	D	0.425	neutral	N	0.442039603	None	None	N
K/V	0.9064	likely_pathogenic	0.8354	pathogenic	0.289	Stabilizing	0.987	D	0.476	neutral	None	None	None	None	N
K/W	0.9631	likely_pathogenic	0.9335	pathogenic	-0.127	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/Y	0.954	likely_pathogenic	0.9209	pathogenic	0.195	Stabilizing	0.996	D	0.504	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.