TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18002	54229;54230;54231	chr2:178605173;178605172;178605171	chr2:179469900;179469899;179469898
N2AB	16361	49306;49307;49308	chr2:178605173;178605172;178605171	chr2:179469900;179469899;179469898
N2A	15434	46525;46526;46527	chr2:178605173;178605172;178605171	chr2:179469900;179469899;179469898
N2B	8937	27034;27035;27036	chr2:178605173;178605172;178605171	chr2:179469900;179469899;179469898
Novex-1	9062	27409;27410;27411	chr2:178605173;178605172;178605171	chr2:179469900;179469899;179469898
Novex-2	9129	27610;27611;27612	chr2:178605173;178605172;178605171	chr2:179469900;179469899;179469898
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-114
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1354
• 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	None	None	0.999	N	0.586	0.374	0.336400405673	gnomAD-4.0.0	1.59397E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86248E-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	0.9599	likely_pathogenic	0.9706	pathogenic	-1.112	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
K/C	0.8972	likely_pathogenic	0.9236	pathogenic	-1.259	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
K/D	0.9916	likely_pathogenic	0.9944	pathogenic	-0.313	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/E	0.8854	likely_pathogenic	0.9139	pathogenic	-0.205	Destabilizing	0.999	D	0.569	neutral	D	0.523689632	None	None	N
K/F	0.9585	likely_pathogenic	0.9689	pathogenic	-1.299	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
K/G	0.9801	likely_pathogenic	0.9859	pathogenic	-1.414	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
K/H	0.6402	likely_pathogenic	0.7104	pathogenic	-1.933	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
K/I	0.8578	likely_pathogenic	0.8814	pathogenic	-0.335	Destabilizing	1.0	D	0.877	deleterious	N	0.492961624	None	None	N
K/L	0.8163	likely_pathogenic	0.8525	pathogenic	-0.335	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
K/M	0.7469	likely_pathogenic	0.784	pathogenic	-0.213	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/N	0.9637	likely_pathogenic	0.9753	pathogenic	-0.679	Destabilizing	1.0	D	0.731	prob.delet.	N	0.493975582	None	None	N
K/P	0.9986	likely_pathogenic	0.9989	pathogenic	-0.569	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
K/Q	0.5228	ambiguous	0.5912	pathogenic	-0.832	Destabilizing	1.0	D	0.719	prob.delet.	N	0.504824909	None	None	N
K/R	0.092	likely_benign	0.1039	benign	-0.635	Destabilizing	0.999	D	0.586	neutral	N	0.494943007	None	None	N
K/S	0.9708	likely_pathogenic	0.9796	pathogenic	-1.471	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
K/T	0.9363	likely_pathogenic	0.9554	pathogenic	-1.152	Destabilizing	1.0	D	0.815	deleterious	N	0.496684607	None	None	N
K/V	0.8207	likely_pathogenic	0.8479	pathogenic	-0.569	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/W	0.9427	likely_pathogenic	0.9608	pathogenic	-1.112	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/Y	0.8966	likely_pathogenic	0.9108	pathogenic	-0.753	Destabilizing	1.0	D	0.857	deleterious	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.