TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31823	95692;95693;95694	chr2:178545643;178545642;178545641	chr2:179410370;179410369;179410368
N2AB	30182	90769;90770;90771	chr2:178545643;178545642;178545641	chr2:179410370;179410369;179410368
N2A	29255	87988;87989;87990	chr2:178545643;178545642;178545641	chr2:179410370;179410369;179410368
N2B	22758	68497;68498;68499	chr2:178545643;178545642;178545641	chr2:179410370;179410369;179410368
Novex-1	22883	68872;68873;68874	chr2:178545643;178545642;178545641	chr2:179410370;179410369;179410368
Novex-2	22950	69073;69074;69075	chr2:178545643;178545642;178545641	chr2:179410370;179410369;179410368
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: Fn3-120
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.2748
• 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/R	rs794729539	-1.034	0.999	N	0.451	0.278	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.87E-06	0
H/R	rs794729539	-1.034	0.999	N	0.451	0.278	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
H/R	rs794729539	-1.034	0.999	N	0.451	0.278	None	gnomAD-4.0.0	2.04499E-05	None	None	None	None	N	None	1.33472E-05	0	None	0	0	None	0	0	2.54292E-05	0	3.20225E-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	0.4608	ambiguous	0.3705	ambiguous	-1.073	Destabilizing	0.993	D	0.588	neutral	None	None	None	None	N
H/C	0.2181	likely_benign	0.1917	benign	-0.361	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
H/D	0.4207	ambiguous	0.3309	benign	-0.741	Destabilizing	0.999	D	0.571	neutral	N	0.47420795	None	None	N
H/E	0.5316	ambiguous	0.4328	ambiguous	-0.64	Destabilizing	0.998	D	0.456	neutral	None	None	None	None	N
H/F	0.3021	likely_benign	0.2801	benign	0.033	Stabilizing	0.996	D	0.582	neutral	None	None	None	None	N
H/G	0.489	ambiguous	0.3951	ambiguous	-1.431	Destabilizing	0.998	D	0.592	neutral	None	None	None	None	N
H/I	0.5388	ambiguous	0.4708	ambiguous	-0.075	Destabilizing	0.991	D	0.662	neutral	None	None	None	None	N
H/K	0.5818	likely_pathogenic	0.4558	ambiguous	-0.924	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
H/L	0.3076	likely_benign	0.2497	benign	-0.075	Destabilizing	0.135	N	0.536	neutral	N	0.493487144	None	None	N
H/M	0.5155	ambiguous	0.4785	ambiguous	-0.195	Destabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	N
H/N	0.1122	likely_benign	0.099	benign	-0.938	Destabilizing	0.997	D	0.455	neutral	N	0.443231682	None	None	N
H/P	0.9005	likely_pathogenic	0.8542	pathogenic	-0.389	Destabilizing	0.999	D	0.684	prob.neutral	N	0.504704215	None	None	N
H/Q	0.3086	likely_benign	0.2429	benign	-0.684	Destabilizing	0.999	D	0.465	neutral	N	0.455102114	None	None	N
H/R	0.3434	ambiguous	0.2508	benign	-1.271	Destabilizing	0.999	D	0.451	neutral	N	0.46029729	None	None	N
H/S	0.2635	likely_benign	0.2142	benign	-1.048	Destabilizing	0.998	D	0.542	neutral	None	None	None	None	N
H/T	0.328	likely_benign	0.2574	benign	-0.848	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
H/V	0.4449	ambiguous	0.3748	ambiguous	-0.389	Destabilizing	0.971	D	0.65	neutral	None	None	None	None	N
H/W	0.5298	ambiguous	0.4884	ambiguous	0.291	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
H/Y	0.1124	likely_benign	0.1045	benign	0.433	Stabilizing	0.997	D	0.489	neutral	N	0.435689634	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.