TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16039	48340;48341;48342	chr2:178616774;178616773;178616772	chr2:179481501;179481500;179481499
N2AB	14398	43417;43418;43419	chr2:178616774;178616773;178616772	chr2:179481501;179481500;179481499
N2A	13471	40636;40637;40638	chr2:178616774;178616773;178616772	chr2:179481501;179481500;179481499
N2B	6974	21145;21146;21147	chr2:178616774;178616773;178616772	chr2:179481501;179481500;179481499
Novex-1	7099	21520;21521;21522	chr2:178616774;178616773;178616772	chr2:179481501;179481500;179481499
Novex-2	7166	21721;21722;21723	chr2:178616774;178616773;178616772	chr2:179481501;179481500;179481499
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-109
• Domain position: 72
• Structural Position: 161
• Q(SASA): 0.1343
• 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
N/K	None	None	1.0	D	0.727	0.571	0.312306559268	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
N/A	0.9959	likely_pathogenic	0.9979	pathogenic	-0.584	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
N/C	0.965	likely_pathogenic	0.981	pathogenic	0.014	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/D	0.9679	likely_pathogenic	0.9788	pathogenic	-1.228	Destabilizing	0.999	D	0.588	neutral	D	0.661005114	None	None	I
N/E	0.995	likely_pathogenic	0.9968	pathogenic	-1.157	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	I
N/F	0.9989	likely_pathogenic	0.9993	pathogenic	-0.59	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
N/G	0.981	likely_pathogenic	0.9866	pathogenic	-0.883	Destabilizing	0.999	D	0.545	neutral	None	None	None	None	I
N/H	0.9719	likely_pathogenic	0.981	pathogenic	-0.874	Destabilizing	1.0	D	0.739	prob.delet.	D	0.66343	None	None	I
N/I	0.9927	likely_pathogenic	0.9962	pathogenic	0.156	Stabilizing	1.0	D	0.728	prob.delet.	D	0.664156602	None	None	I
N/K	0.9964	likely_pathogenic	0.9977	pathogenic	-0.247	Destabilizing	1.0	D	0.727	prob.delet.	D	0.662507114	None	None	I
N/L	0.9877	likely_pathogenic	0.9919	pathogenic	0.156	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/M	0.9914	likely_pathogenic	0.995	pathogenic	0.718	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
N/P	0.9978	likely_pathogenic	0.9984	pathogenic	-0.061	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
N/Q	0.9967	likely_pathogenic	0.998	pathogenic	-1.027	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
N/R	0.996	likely_pathogenic	0.9975	pathogenic	-0.223	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
N/S	0.8952	likely_pathogenic	0.934	pathogenic	-0.785	Destabilizing	0.999	D	0.559	neutral	D	0.597250923	None	None	I
N/T	0.9531	likely_pathogenic	0.9731	pathogenic	-0.552	Destabilizing	0.999	D	0.695	prob.neutral	D	0.661124163	None	None	I
N/V	0.992	likely_pathogenic	0.9957	pathogenic	-0.061	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
N/W	0.9994	likely_pathogenic	0.9996	pathogenic	-0.459	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
N/Y	0.9825	likely_pathogenic	0.9875	pathogenic	-0.167	Destabilizing	1.0	D	0.75	deleterious	D	0.66343	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.