TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8888	26887;26888;26889	chr2:178713996;178713995;178713994	chr2:179578723;179578722;179578721
N2AB	8571	25936;25937;25938	chr2:178713996;178713995;178713994	chr2:179578723;179578722;179578721
N2A	7644	23155;23156;23157	chr2:178713996;178713995;178713994	chr2:179578723;179578722;179578721
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-74
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.4739
• 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	0.959	N	0.525	0.196	0.407767136052	gnomAD-4.0.0	1.59166E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85878E-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	0.7817	likely_pathogenic	0.7725	pathogenic	-0.713	Destabilizing	0.759	D	0.509	neutral	None	None	None	None	N
K/C	0.87	likely_pathogenic	0.8686	pathogenic	-0.928	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
K/D	0.9131	likely_pathogenic	0.9115	pathogenic	-0.442	Destabilizing	0.046	N	0.354	neutral	None	None	None	None	N
K/E	0.5234	ambiguous	0.4968	ambiguous	-0.326	Destabilizing	0.704	D	0.574	neutral	N	0.453942613	None	None	N
K/F	0.9357	likely_pathogenic	0.9423	pathogenic	-0.518	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	N
K/G	0.8797	likely_pathogenic	0.8825	pathogenic	-1.075	Destabilizing	0.863	D	0.527	neutral	None	None	None	None	N
K/H	0.4487	ambiguous	0.4465	ambiguous	-1.449	Destabilizing	0.991	D	0.574	neutral	None	None	None	None	N
K/I	0.6282	likely_pathogenic	0.6299	pathogenic	0.227	Stabilizing	0.991	D	0.618	neutral	None	None	None	None	N
K/L	0.6696	likely_pathogenic	0.6756	pathogenic	0.227	Stabilizing	0.969	D	0.556	neutral	None	None	None	None	N
K/M	0.4604	ambiguous	0.4521	ambiguous	0.153	Stabilizing	0.999	D	0.569	neutral	D	0.527709653	None	None	N
K/N	0.7795	likely_pathogenic	0.7722	pathogenic	-0.674	Destabilizing	0.061	N	0.324	neutral	N	0.509027891	None	None	N
K/P	0.9884	likely_pathogenic	0.9893	pathogenic	-0.057	Destabilizing	0.991	D	0.579	neutral	None	None	None	None	N
K/Q	0.2518	likely_benign	0.242	benign	-0.802	Destabilizing	0.959	D	0.531	neutral	N	0.49080749	None	None	N
K/R	0.1043	likely_benign	0.1103	benign	-0.653	Destabilizing	0.959	D	0.525	neutral	N	0.47976099	None	None	N
K/S	0.7913	likely_pathogenic	0.778	pathogenic	-1.362	Destabilizing	0.373	N	0.327	neutral	None	None	None	None	N
K/T	0.4228	ambiguous	0.3903	ambiguous	-1.037	Destabilizing	0.852	D	0.53	neutral	N	0.46723441	None	None	N
K/V	0.6135	likely_pathogenic	0.6183	pathogenic	-0.057	Destabilizing	0.969	D	0.584	neutral	None	None	None	None	N
K/W	0.8802	likely_pathogenic	0.8996	pathogenic	-0.377	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	N
K/Y	0.8182	likely_pathogenic	0.8302	pathogenic	-0.033	Destabilizing	0.997	D	0.603	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.