TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17004	51235;51236;51237	chr2:178611119;178611118;178611117	chr2:179475846;179475845;179475844
N2AB	15363	46312;46313;46314	chr2:178611119;178611118;178611117	chr2:179475846;179475845;179475844
N2A	14436	43531;43532;43533	chr2:178611119;178611118;178611117	chr2:179475846;179475845;179475844
N2B	7939	24040;24041;24042	chr2:178611119;178611118;178611117	chr2:179475846;179475845;179475844
Novex-1	8064	24415;24416;24417	chr2:178611119;178611118;178611117	chr2:179475846;179475845;179475844
Novex-2	8131	24616;24617;24618	chr2:178611119;178611118;178611117	chr2:179475846;179475845;179475844
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-111
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.7672
• 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/N	rs755153359	0.689	0.92	N	0.384	0.198	0.264081493735	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/N	rs755153359	0.689	0.92	N	0.384	0.198	0.264081493735	gnomAD-4.0.0	9.55907E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.71716E-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	0.3447	ambiguous	0.3271	benign	0.023	Stabilizing	0.759	D	0.375	neutral	None	None	None	None	N
K/C	0.6341	likely_pathogenic	0.6104	pathogenic	0.216	Stabilizing	0.999	D	0.409	neutral	None	None	None	None	N
K/D	0.522	ambiguous	0.5004	ambiguous	0.041	Stabilizing	0.939	D	0.398	neutral	None	None	None	None	N
K/E	0.1611	likely_benign	0.1587	benign	0.068	Stabilizing	0.92	D	0.385	neutral	N	0.4825785	None	None	N
K/F	0.6907	likely_pathogenic	0.6979	pathogenic	0.01	Stabilizing	0.982	D	0.432	neutral	None	None	None	None	N
K/G	0.4449	ambiguous	0.4193	ambiguous	-0.242	Destabilizing	0.939	D	0.429	neutral	None	None	None	None	N
K/H	0.2605	likely_benign	0.2472	benign	-0.689	Destabilizing	0.997	D	0.405	neutral	None	None	None	None	N
K/I	0.278	likely_benign	0.2876	benign	0.662	Stabilizing	0.964	D	0.41	neutral	None	None	None	None	N
K/L	0.3457	ambiguous	0.3378	benign	0.662	Stabilizing	0.759	D	0.391	neutral	None	None	None	None	N
K/M	0.2031	likely_benign	0.2012	benign	0.546	Stabilizing	0.509	D	0.288	neutral	N	0.513033033	None	None	N
K/N	0.3032	likely_benign	0.2947	benign	0.45	Stabilizing	0.92	D	0.384	neutral	N	0.512852299	None	None	N
K/P	0.9055	likely_pathogenic	0.8937	pathogenic	0.478	Stabilizing	0.991	D	0.403	neutral	None	None	None	None	N
K/Q	0.1168	likely_benign	0.1141	benign	0.281	Stabilizing	0.92	D	0.411	neutral	N	0.504027163	None	None	N
K/R	0.0863	likely_benign	0.0815	benign	-0.074	Destabilizing	0.015	N	0.131	neutral	N	0.475718278	None	None	N
K/S	0.3388	likely_benign	0.3258	benign	-0.007	Destabilizing	0.373	N	0.173	neutral	None	None	None	None	N
K/T	0.1404	likely_benign	0.1354	benign	0.178	Stabilizing	0.852	D	0.387	neutral	N	0.455894005	None	None	N
K/V	0.2781	likely_benign	0.2847	benign	0.478	Stabilizing	0.884	D	0.424	neutral	None	None	None	None	N
K/W	0.7041	likely_pathogenic	0.7027	pathogenic	0.017	Stabilizing	0.999	D	0.443	neutral	None	None	None	None	N
K/Y	0.5772	likely_pathogenic	0.5819	pathogenic	0.336	Stabilizing	0.997	D	0.431	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.