TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32867	98824;98825;98826	chr2:178539466;178539465;178539464	chr2:179404193;179404192;179404191
N2AB	31226	93901;93902;93903	chr2:178539466;178539465;178539464	chr2:179404193;179404192;179404191
N2A	30299	91120;91121;91122	chr2:178539466;178539465;178539464	chr2:179404193;179404192;179404191
N2B	23802	71629;71630;71631	chr2:178539466;178539465;178539464	chr2:179404193;179404192;179404191
Novex-1	23927	72004;72005;72006	chr2:178539466;178539465;178539464	chr2:179404193;179404192;179404191
Novex-2	23994	72205;72206;72207	chr2:178539466;178539465;178539464	chr2:179404193;179404192;179404191
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-127
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2253
• 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
H/L	None	None	1.0	N	0.712	0.52	0.758974145601	gnomAD-4.0.0	4.77351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71634E-06	0	3.02407E-05

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
H/A	0.661	likely_pathogenic	0.5648	pathogenic	-2.091	Highly Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
H/C	0.2855	likely_benign	0.2237	benign	-1.125	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
H/D	0.6667	likely_pathogenic	0.5391	ambiguous	-1.957	Destabilizing	1.0	D	0.663	neutral	N	0.495911373	None	None	N
H/E	0.6641	likely_pathogenic	0.5899	pathogenic	-1.742	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
H/F	0.302	likely_benign	0.2855	benign	-0.031	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
H/G	0.7769	likely_pathogenic	0.6714	pathogenic	-2.502	Highly Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
H/I	0.4613	ambiguous	0.3859	ambiguous	-0.845	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
H/K	0.6915	likely_pathogenic	0.6264	pathogenic	-1.222	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
H/L	0.1886	likely_benign	0.1568	benign	-0.845	Destabilizing	1.0	D	0.712	prob.delet.	N	0.441231526	None	None	N
H/M	0.6498	likely_pathogenic	0.5977	pathogenic	-1.021	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
H/N	0.2956	likely_benign	0.2296	benign	-1.989	Destabilizing	0.999	D	0.571	neutral	N	0.448829502	None	None	N
H/P	0.9238	likely_pathogenic	0.8683	pathogenic	-1.255	Destabilizing	1.0	D	0.72	prob.delet.	N	0.474736146	None	None	N
H/Q	0.4644	ambiguous	0.3937	ambiguous	-1.558	Destabilizing	1.0	D	0.701	prob.neutral	N	0.375102535	None	None	N
H/R	0.3638	ambiguous	0.2967	benign	-1.348	Destabilizing	1.0	D	0.674	neutral	N	0.429321022	None	None	N
H/S	0.4965	ambiguous	0.4016	ambiguous	-2.168	Highly Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
H/T	0.587	likely_pathogenic	0.4971	ambiguous	-1.837	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
H/V	0.4376	ambiguous	0.3675	ambiguous	-1.255	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
H/W	0.4872	ambiguous	0.4428	ambiguous	0.607	Stabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
H/Y	0.1142	likely_benign	0.0996	benign	0.298	Stabilizing	0.999	D	0.576	neutral	N	0.417162588	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.