TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29878	89857;89858;89859	chr2:178553268;178553267;178553266	chr2:179417995;179417994;179417993
N2AB	28237	84934;84935;84936	chr2:178553268;178553267;178553266	chr2:179417995;179417994;179417993
N2A	27310	82153;82154;82155	chr2:178553268;178553267;178553266	chr2:179417995;179417994;179417993
N2B	20813	62662;62663;62664	chr2:178553268;178553267;178553266	chr2:179417995;179417994;179417993
Novex-1	20938	63037;63038;63039	chr2:178553268;178553267;178553266	chr2:179417995;179417994;179417993
Novex-2	21005	63238;63239;63240	chr2:178553268;178553267;178553266	chr2:179417995;179417994;179417993
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-147
• Domain position: 37
• Structural Position: 55
• Q(SASA): 0.6591
• 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/E	None	None	0.989	N	0.515	0.331	0.367612772649	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	0	0
K/N	rs748356210	None	0.998	N	0.537	0.357	0.335910606209	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.3059	likely_benign	0.2903	benign	-0.465	Destabilizing	0.996	D	0.535	neutral	None	None	None	None	N
K/C	0.6274	likely_pathogenic	0.5822	pathogenic	-0.426	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
K/D	0.4644	ambiguous	0.4333	ambiguous	-0.102	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	N
K/E	0.1471	likely_benign	0.134	benign	-0.008	Destabilizing	0.989	D	0.515	neutral	N	0.421600908	None	None	N
K/F	0.6945	likely_pathogenic	0.6438	pathogenic	-0.244	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
K/G	0.3791	ambiguous	0.3614	ambiguous	-0.819	Destabilizing	0.999	D	0.483	neutral	None	None	None	None	N
K/H	0.2717	likely_benign	0.2606	benign	-1.259	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	N
K/I	0.2504	likely_benign	0.2262	benign	0.441	Stabilizing	1.0	D	0.648	neutral	None	None	None	None	N
K/L	0.3113	likely_benign	0.2839	benign	0.441	Stabilizing	0.999	D	0.483	neutral	None	None	None	None	N
K/M	0.1892	likely_benign	0.1717	benign	0.356	Stabilizing	1.0	D	0.559	neutral	N	0.468280134	None	None	N
K/N	0.2837	likely_benign	0.2605	benign	-0.335	Destabilizing	0.998	D	0.537	neutral	N	0.445056557	None	None	N
K/P	0.8702	likely_pathogenic	0.8467	pathogenic	0.17	Stabilizing	1.0	D	0.57	neutral	None	None	None	None	N
K/Q	0.1105	likely_benign	0.109	benign	-0.417	Destabilizing	0.997	D	0.543	neutral	N	0.436781004	None	None	N
K/R	0.0834	likely_benign	0.0811	benign	-0.603	Destabilizing	0.217	N	0.299	neutral	N	0.430703181	None	None	N
K/S	0.3449	ambiguous	0.3169	benign	-0.952	Destabilizing	0.996	D	0.516	neutral	None	None	None	None	N
K/T	0.1465	likely_benign	0.1367	benign	-0.655	Destabilizing	0.998	D	0.527	neutral	N	0.446499352	None	None	N
K/V	0.2381	likely_benign	0.2182	benign	0.17	Stabilizing	0.999	D	0.583	neutral	None	None	None	None	N
K/W	0.7195	likely_pathogenic	0.6815	pathogenic	-0.148	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/Y	0.5273	ambiguous	0.4865	ambiguous	0.152	Stabilizing	1.0	D	0.575	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.