TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9075	27448;27449;27450	chr2:178712802;178712801;178712800	chr2:179577529;179577528;179577527
N2AB	8758	26497;26498;26499	chr2:178712802;178712801;178712800	chr2:179577529;179577528;179577527
N2A	7831	23716;23717;23718	chr2:178712802;178712801;178712800	chr2:179577529;179577528;179577527
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-76
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.3076
• 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
E/K	rs1560584120	None	0.801	N	0.554	0.238	0.348983352498	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79895E-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
E/A	0.2063	likely_benign	0.2034	benign	-0.939	Destabilizing	0.454	N	0.433	neutral	N	0.501581844	None	None	N
E/C	0.8737	likely_pathogenic	0.8808	pathogenic	-0.527	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	N
E/D	0.4387	ambiguous	0.4462	ambiguous	-1.377	Destabilizing	0.891	D	0.533	neutral	N	0.506950378	None	None	N
E/F	0.7256	likely_pathogenic	0.7644	pathogenic	-0.792	Destabilizing	0.949	D	0.634	neutral	None	None	None	None	N
E/G	0.3092	likely_benign	0.3169	benign	-1.312	Destabilizing	0.891	D	0.589	neutral	N	0.511702837	None	None	N
E/H	0.4905	ambiguous	0.5189	ambiguous	-1.093	Destabilizing	0.991	D	0.557	neutral	None	None	None	None	N
E/I	0.3282	likely_benign	0.3361	benign	0.084	Stabilizing	0.728	D	0.583	neutral	None	None	None	None	N
E/K	0.1367	likely_benign	0.1426	benign	-0.683	Destabilizing	0.801	D	0.554	neutral	N	0.48688175	None	None	N
E/L	0.4291	ambiguous	0.4308	ambiguous	0.084	Stabilizing	0.525	D	0.498	neutral	None	None	None	None	N
E/M	0.423	ambiguous	0.4272	ambiguous	0.667	Stabilizing	0.325	N	0.493	neutral	None	None	None	None	N
E/N	0.4856	ambiguous	0.4847	ambiguous	-1.082	Destabilizing	0.915	D	0.518	neutral	None	None	None	None	N
E/P	0.9783	likely_pathogenic	0.9851	pathogenic	-0.236	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	N
E/Q	0.1197	likely_benign	0.1211	benign	-0.933	Destabilizing	0.891	D	0.527	neutral	N	0.516127222	None	None	N
E/R	0.2276	likely_benign	0.2489	benign	-0.601	Destabilizing	0.915	D	0.541	neutral	None	None	None	None	N
E/S	0.2715	likely_benign	0.2668	benign	-1.51	Destabilizing	0.525	D	0.511	neutral	None	None	None	None	N
E/T	0.2412	likely_benign	0.2406	benign	-1.178	Destabilizing	0.029	N	0.311	neutral	None	None	None	None	N
E/V	0.1828	likely_benign	0.1815	benign	-0.236	Destabilizing	0.005	N	0.479	neutral	N	0.441496177	None	None	N
E/W	0.903	likely_pathogenic	0.9257	pathogenic	-0.705	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
E/Y	0.6616	likely_pathogenic	0.7038	pathogenic	-0.542	Destabilizing	0.991	D	0.614	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.