TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32469	97630;97631;97632	chr2:178542351;178542350;178542349	chr2:179407078;179407077;179407076
N2AB	30828	92707;92708;92709	chr2:178542351;178542350;178542349	chr2:179407078;179407077;179407076
N2A	29901	89926;89927;89928	chr2:178542351;178542350;178542349	chr2:179407078;179407077;179407076
N2B	23404	70435;70436;70437	chr2:178542351;178542350;178542349	chr2:179407078;179407077;179407076
Novex-1	23529	70810;70811;70812	chr2:178542351;178542350;178542349	chr2:179407078;179407077;179407076
Novex-2	23596	71011;71012;71013	chr2:178542351;178542350;178542349	chr2:179407078;179407077;179407076
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-124
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.4862
• 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	rs1280768790	-0.039	0.999	N	0.601	0.421	0.485846224565	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs1280768790	-0.039	0.999	N	0.601	0.421	0.485846224565	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1280768790	-0.039	0.999	N	0.601	0.421	0.485846224565	gnomAD-4.0.0	3.71895E-06	None	None	None	None	N	None	2.67037E-05	0	None	0	0	None	0	0	3.39074E-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	0.3788	ambiguous	0.2906	benign	-0.947	Destabilizing	0.999	D	0.703	prob.neutral	N	0.496109312	None	None	N
E/C	0.9285	likely_pathogenic	0.8989	pathogenic	-0.619	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/D	0.4308	ambiguous	0.3498	ambiguous	-1.35	Destabilizing	0.999	D	0.476	neutral	N	0.494779412	None	None	N
E/F	0.9499	likely_pathogenic	0.9188	pathogenic	-0.503	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/G	0.525	ambiguous	0.4284	ambiguous	-1.334	Destabilizing	1.0	D	0.767	deleterious	N	0.500984384	None	None	N
E/H	0.8164	likely_pathogenic	0.7206	pathogenic	-0.975	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
E/I	0.6882	likely_pathogenic	0.6097	pathogenic	0.122	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.4249	ambiguous	0.3123	benign	-1.215	Destabilizing	0.999	D	0.601	neutral	N	0.481902169	None	None	N
E/L	0.7762	likely_pathogenic	0.6849	pathogenic	0.122	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/M	0.7409	likely_pathogenic	0.6582	pathogenic	0.717	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/N	0.6222	likely_pathogenic	0.521	ambiguous	-1.525	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/P	0.9013	likely_pathogenic	0.8467	pathogenic	-0.213	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.2548	likely_benign	0.199	benign	-1.344	Destabilizing	1.0	D	0.619	neutral	N	0.485714058	None	None	N
E/R	0.5706	likely_pathogenic	0.4397	ambiguous	-0.975	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.4473	ambiguous	0.3603	ambiguous	-1.918	Destabilizing	0.999	D	0.642	neutral	None	None	None	None	N
E/T	0.4387	ambiguous	0.3505	ambiguous	-1.606	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/V	0.5153	ambiguous	0.4274	ambiguous	-0.213	Destabilizing	1.0	D	0.801	deleterious	N	0.48560238	None	None	N
E/W	0.9831	likely_pathogenic	0.9708	pathogenic	-0.39	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.9045	likely_pathogenic	0.8512	pathogenic	-0.328	Destabilizing	1.0	D	0.775	deleterious	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.