TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3942	12049;12050;12051	chr2:178741409;178741408;178741407	chr2:179606136;179606135;179606134
N2AB	3625	11098;11099;11100	chr2:178741409;178741408;178741407	chr2:179606136;179606135;179606134
N2A	None	None	chr2:None	chr2:None
N2B	3579	10960;10961;10962	chr2:178741409;178741408;178741407	chr2:179606136;179606135;179606134
Novex-1	3704	11335;11336;11337	chr2:178741409;178741408;178741407	chr2:179606136;179606135;179606134
Novex-2	3771	11536;11537;11538	chr2:178741409;178741408;178741407	chr2:179606136;179606135;179606134
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-28
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6092
• Predicted PPI site: I

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	rs2082461755	None	0.625	N	0.306	0.177	None	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.8226E-04	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	0.3453	ambiguous	0.3667	ambiguous	-0.346	Destabilizing	0.525	D	0.345	neutral	None	None	None	None	I
K/C	0.69	likely_pathogenic	0.7046	pathogenic	-0.456	Destabilizing	0.998	D	0.31	neutral	None	None	None	None	I
K/D	0.559	ambiguous	0.5716	pathogenic	0.094	Stabilizing	0.842	D	0.399	neutral	None	None	None	None	I
K/E	0.1309	likely_benign	0.1363	benign	0.198	Stabilizing	0.625	D	0.306	neutral	N	0.509764227	None	None	I
K/F	0.7712	likely_pathogenic	0.7835	pathogenic	0.017	Stabilizing	0.974	D	0.353	neutral	None	None	None	None	I
K/G	0.4047	ambiguous	0.4297	ambiguous	-0.702	Destabilizing	0.842	D	0.379	neutral	None	None	None	None	I
K/H	0.3347	likely_benign	0.34	benign	-0.932	Destabilizing	0.037	N	0.179	neutral	None	None	None	None	I
K/I	0.3981	ambiguous	0.4041	ambiguous	0.567	Stabilizing	0.728	D	0.39	neutral	None	None	None	None	I
K/L	0.356	ambiguous	0.375	ambiguous	0.567	Stabilizing	0.525	D	0.342	neutral	None	None	None	None	I
K/M	0.2504	likely_benign	0.257	benign	0.287	Stabilizing	0.966	D	0.357	neutral	D	0.584213283	None	None	I
K/N	0.382	ambiguous	0.3996	ambiguous	-0.282	Destabilizing	0.801	D	0.303	neutral	N	0.511636613	None	None	I
K/P	0.7723	likely_pathogenic	0.7798	pathogenic	0.294	Stabilizing	0.974	D	0.382	neutral	None	None	None	None	I
K/Q	0.1285	likely_benign	0.1329	benign	-0.326	Destabilizing	0.801	D	0.349	neutral	N	0.500910637	None	None	I
K/R	0.0839	likely_benign	0.0835	benign	-0.474	Destabilizing	0.012	N	0.185	neutral	N	0.502849283	None	None	I
K/S	0.3982	ambiguous	0.4131	ambiguous	-0.913	Destabilizing	0.728	D	0.287	neutral	None	None	None	None	I
K/T	0.1813	likely_benign	0.187	benign	-0.606	Destabilizing	0.051	N	0.155	neutral	N	0.502918738	None	None	I
K/V	0.3553	ambiguous	0.3681	ambiguous	0.294	Stabilizing	0.029	N	0.155	neutral	None	None	None	None	I
K/W	0.7341	likely_pathogenic	0.7277	pathogenic	0.119	Stabilizing	0.998	D	0.341	neutral	None	None	None	None	I
K/Y	0.625	likely_pathogenic	0.6247	pathogenic	0.394	Stabilizing	0.949	D	0.352	neutral	None	None	None	None	I

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.