TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8252	24979;24980;24981	chr2:178718352;178718351;178718350	chr2:179583079;179583078;179583077
N2AB	7935	24028;24029;24030	chr2:178718352;178718351;178718350	chr2:179583079;179583078;179583077
N2A	7008	21247;21248;21249	chr2:178718352;178718351;178718350	chr2:179583079;179583078;179583077
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-67
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2071
• 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
D/A	rs762054067	None	0.543	N	0.483	0.333	0.453119318887	gnomAD-4.0.0	6.84275E-07	None	None	None	None	N	None	2.98918E-05	0	None	0	0	None	0	0	0	0	0
D/E	rs764248656	0.095	0.543	N	0.243	0.11	0.225215365344	gnomAD-2.1.1	1.50167E-04	None	None	None	None	N	None	0	0	None	0	2.04939E-03	None	0	None	0	0	2.81611E-04
D/E	rs764248656	0.095	0.543	N	0.243	0.11	0.225215365344	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	0	0	0	0	2.12273E-03	None	0	0	0	0	0
D/E	rs764248656	0.095	0.543	N	0.243	0.11	0.225215365344	gnomAD-4.0.0	4.21391E-05	None	None	None	None	N	None	0	0	None	0	1.24833E-03	None	0	0	0	2.19616E-05	1.60046E-04
D/G	rs762054067	-0.513	0.989	N	0.587	0.506	0.433936292671	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
D/G	rs762054067	-0.513	0.989	N	0.587	0.506	0.433936292671	gnomAD-4.0.0	6.84275E-07	None	None	None	None	N	None	0	0	None	0	2.51953E-05	None	0	0	0	0	0
D/H	rs1173109154	0.332	1.0	D	0.699	0.463	0.518312163451	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	0	0	None	0	1.0247E-04	None	0	None	0	0	0
D/H	rs1173109154	0.332	1.0	D	0.699	0.463	0.518312163451	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92753E-04	None	0	0	0	0	0
D/H	rs1173109154	0.332	1.0	D	0.699	0.463	0.518312163451	gnomAD-4.0.0	1.85926E-06	None	None	None	None	N	None	0	0	None	0	6.68479E-05	None	0	0	0	0	0
D/V	None	None	0.997	N	0.749	0.483	0.687860213003	gnomAD-4.0.0	6.84275E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99549E-07	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
D/A	0.5108	ambiguous	0.3761	ambiguous	-0.467	Destabilizing	0.543	D	0.483	neutral	N	0.490247343	None	None	N
D/C	0.9661	likely_pathogenic	0.9284	pathogenic	-0.152	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
D/E	0.62	likely_pathogenic	0.4976	ambiguous	-0.58	Destabilizing	0.543	D	0.243	neutral	N	0.481983027	None	None	N
D/F	0.9593	likely_pathogenic	0.9102	pathogenic	0.075	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
D/G	0.4997	ambiguous	0.4025	ambiguous	-0.891	Destabilizing	0.989	D	0.587	neutral	N	0.504268018	None	None	N
D/H	0.8494	likely_pathogenic	0.7648	pathogenic	-0.248	Destabilizing	1.0	D	0.699	prob.neutral	D	0.533728579	None	None	N
D/I	0.9251	likely_pathogenic	0.8089	pathogenic	0.681	Stabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
D/K	0.9098	likely_pathogenic	0.855	pathogenic	-0.495	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
D/L	0.9212	likely_pathogenic	0.8347	pathogenic	0.681	Stabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
D/M	0.96	likely_pathogenic	0.9083	pathogenic	1.181	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
D/N	0.3128	likely_benign	0.2461	benign	-0.953	Destabilizing	0.998	D	0.632	neutral	N	0.506216575	None	None	N
D/P	0.9967	likely_pathogenic	0.992	pathogenic	0.324	Stabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
D/Q	0.8685	likely_pathogenic	0.7841	pathogenic	-0.727	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	N
D/R	0.9331	likely_pathogenic	0.8819	pathogenic	-0.355	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
D/S	0.4347	ambiguous	0.3399	benign	-1.366	Destabilizing	0.983	D	0.503	neutral	None	None	None	None	N
D/T	0.7702	likely_pathogenic	0.6179	pathogenic	-1.004	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
D/V	0.7803	likely_pathogenic	0.5741	pathogenic	0.324	Stabilizing	0.997	D	0.749	deleterious	N	0.516721868	None	None	N
D/W	0.9964	likely_pathogenic	0.9899	pathogenic	0.188	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
D/Y	0.821	likely_pathogenic	0.6937	pathogenic	0.326	Stabilizing	1.0	D	0.786	deleterious	D	0.533982068	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.