TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28444	85555;85556;85557	chr2:178560802;178560801;178560800	chr2:179425529;179425528;179425527
N2AB	26803	80632;80633;80634	chr2:178560802;178560801;178560800	chr2:179425529;179425528;179425527
N2A	25876	77851;77852;77853	chr2:178560802;178560801;178560800	chr2:179425529;179425528;179425527
N2B	19379	58360;58361;58362	chr2:178560802;178560801;178560800	chr2:179425529;179425528;179425527
Novex-1	19504	58735;58736;58737	chr2:178560802;178560801;178560800	chr2:179425529;179425528;179425527
Novex-2	19571	58936;58937;58938	chr2:178560802;178560801;178560800	chr2:179425529;179425528;179425527
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-143
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.6583
• 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/D	None	None	0.958	N	0.61	0.382	0.362758974969	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.2889	likely_benign	0.2847	benign	-0.876	Destabilizing	0.968	D	0.683	prob.neutral	None	None	None	None	I
N/C	0.2924	likely_benign	0.2949	benign	0.017	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
N/D	0.2532	likely_benign	0.2263	benign	-0.512	Destabilizing	0.958	D	0.61	neutral	N	0.500113735	None	None	I
N/E	0.527	ambiguous	0.4795	ambiguous	-0.46	Destabilizing	0.968	D	0.639	neutral	None	None	None	None	I
N/F	0.5226	ambiguous	0.4879	ambiguous	-0.819	Destabilizing	0.995	D	0.739	prob.delet.	None	None	None	None	I
N/G	0.402	ambiguous	0.396	ambiguous	-1.169	Destabilizing	0.968	D	0.584	neutral	None	None	None	None	I
N/H	0.0999	likely_benign	0.0946	benign	-1.018	Destabilizing	0.142	N	0.35	neutral	D	0.52526678	None	None	I
N/I	0.1869	likely_benign	0.1781	benign	-0.149	Destabilizing	0.994	D	0.747	deleterious	N	0.491657492	None	None	I
N/K	0.3318	likely_benign	0.2915	benign	-0.227	Destabilizing	0.958	D	0.656	neutral	N	0.515548432	None	None	I
N/L	0.2259	likely_benign	0.2118	benign	-0.149	Destabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	I
N/M	0.3438	ambiguous	0.3344	benign	0.406	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
N/P	0.6027	likely_pathogenic	0.5576	ambiguous	-0.363	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
N/Q	0.3551	ambiguous	0.3331	benign	-0.881	Destabilizing	0.991	D	0.703	prob.neutral	None	None	None	None	I
N/R	0.3428	ambiguous	0.2949	benign	-0.184	Destabilizing	0.991	D	0.671	neutral	None	None	None	None	I
N/S	0.1033	likely_benign	0.1022	benign	-0.761	Destabilizing	0.958	D	0.583	neutral	N	0.502464491	None	None	I
N/T	0.134	likely_benign	0.1303	benign	-0.528	Destabilizing	0.979	D	0.659	neutral	N	0.47389381	None	None	I
N/V	0.2258	likely_benign	0.2165	benign	-0.363	Destabilizing	0.995	D	0.739	prob.delet.	None	None	None	None	I
N/W	0.7586	likely_pathogenic	0.7344	pathogenic	-0.577	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
N/Y	0.1582	likely_benign	0.1446	benign	-0.381	Destabilizing	0.976	D	0.73	prob.delet.	N	0.506154123	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.