TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19083	57472;57473;57474	chr2:178597923;178597922;178597921	chr2:179462650;179462649;179462648
N2AB	17442	52549;52550;52551	chr2:178597923;178597922;178597921	chr2:179462650;179462649;179462648
N2A	16515	49768;49769;49770	chr2:178597923;178597922;178597921	chr2:179462650;179462649;179462648
N2B	10018	30277;30278;30279	chr2:178597923;178597922;178597921	chr2:179462650;179462649;179462648
Novex-1	10143	30652;30653;30654	chr2:178597923;178597922;178597921	chr2:179462650;179462649;179462648
Novex-2	10210	30853;30854;30855	chr2:178597923;178597922;178597921	chr2:179462650;179462649;179462648
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-26
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.058
• 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
M/I	None	None	None	N	0.105	0.07	0.415564226483	gnomAD-4.0.0	1.3689E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9964E-07	0	1.65717E-05
M/R	None	None	0.475	N	0.658	0.2	0.533567079455	gnomAD-4.0.0	1.36887E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-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
M/A	0.6909	likely_pathogenic	0.6961	pathogenic	-2.163	Highly Destabilizing	0.001	N	0.356	neutral	None	None	None	None	N
M/C	0.8012	likely_pathogenic	0.7768	pathogenic	-2.296	Highly Destabilizing	0.928	D	0.601	neutral	None	None	None	None	N
M/D	0.9975	likely_pathogenic	0.9975	pathogenic	-2.315	Highly Destabilizing	0.546	D	0.757	deleterious	None	None	None	None	N
M/E	0.9791	likely_pathogenic	0.9776	pathogenic	-2.092	Highly Destabilizing	0.372	N	0.646	neutral	None	None	None	None	N
M/F	0.8409	likely_pathogenic	0.8589	pathogenic	-0.675	Destabilizing	0.372	N	0.567	neutral	None	None	None	None	N
M/G	0.9452	likely_pathogenic	0.9447	pathogenic	-2.58	Highly Destabilizing	0.109	N	0.61	neutral	None	None	None	None	N
M/H	0.9917	likely_pathogenic	0.9909	pathogenic	-2.32	Highly Destabilizing	0.928	D	0.644	neutral	None	None	None	None	N
M/I	0.5959	likely_pathogenic	0.5829	pathogenic	-0.954	Destabilizing	None	N	0.105	neutral	N	0.406518733	None	None	N
M/K	0.9558	likely_pathogenic	0.9492	pathogenic	-1.469	Destabilizing	0.309	N	0.615	neutral	N	0.502429127	None	None	N
M/L	0.3725	ambiguous	0.3649	ambiguous	-0.954	Destabilizing	0.006	N	0.191	neutral	N	0.444244828	None	None	N
M/N	0.9584	likely_pathogenic	0.9542	pathogenic	-1.86	Destabilizing	0.808	D	0.711	prob.delet.	None	None	None	None	N
M/P	0.8777	likely_pathogenic	0.891	pathogenic	-1.344	Destabilizing	0.546	D	0.68	prob.neutral	None	None	None	None	N
M/Q	0.902	likely_pathogenic	0.8948	pathogenic	-1.532	Destabilizing	0.546	D	0.594	neutral	None	None	None	None	N
M/R	0.9577	likely_pathogenic	0.9532	pathogenic	-1.656	Destabilizing	0.475	N	0.658	prob.neutral	N	0.502949202	None	None	N
M/S	0.9179	likely_pathogenic	0.9139	pathogenic	-2.308	Highly Destabilizing	0.109	N	0.581	neutral	None	None	None	None	N
M/T	0.7839	likely_pathogenic	0.7837	pathogenic	-1.974	Destabilizing	0.156	N	0.555	neutral	N	0.454733968	None	None	N
M/V	0.1896	likely_benign	0.1715	benign	-1.344	Destabilizing	0.001	N	0.105	neutral	N	0.377523978	None	None	N
M/W	0.9927	likely_pathogenic	0.9929	pathogenic	-1.046	Destabilizing	0.98	D	0.563	neutral	None	None	None	None	N
M/Y	0.985	likely_pathogenic	0.9844	pathogenic	-1.039	Destabilizing	0.546	D	0.667	prob.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.