TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1357	4294;4295;4296	chr2:178779013;178779012;178779011	chr2:179643740;179643739;179643738
N2AB	1357	4294;4295;4296	chr2:178779013;178779012;178779011	chr2:179643740;179643739;179643738
N2A	1357	4294;4295;4296	chr2:178779013;178779012;178779011	chr2:179643740;179643739;179643738
N2B	1311	4156;4157;4158	chr2:178779013;178779012;178779011	chr2:179643740;179643739;179643738
Novex-1	1311	4156;4157;4158	chr2:178779013;178779012;178779011	chr2:179643740;179643739;179643738
Novex-2	1311	4156;4157;4158	chr2:178779013;178779012;178779011	chr2:179643740;179643739;179643738
Novex-3	1357	4294;4295;4296	chr2:178779013;178779012;178779011	chr2:179643740;179643739;179643738

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-5
• Domain position: 67
• Structural Position: 148
• Q(SASA): 0.6137
• 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/G	None	None	1.0	N	0.676	0.506	0.391930172978	gnomAD-4.0.0	1.59078E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8569E-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	0.334	likely_benign	0.3235	benign	-0.395	Destabilizing	0.999	D	0.675	neutral	N	0.452450318	None	None	N
E/C	0.9782	likely_pathogenic	0.9776	pathogenic	-0.131	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.3549	ambiguous	0.3572	ambiguous	-0.344	Destabilizing	0.999	D	0.475	neutral	N	0.443016901	None	None	N
E/F	0.9804	likely_pathogenic	0.9813	pathogenic	-0.292	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/G	0.4396	ambiguous	0.4375	ambiguous	-0.581	Destabilizing	1.0	D	0.676	prob.neutral	N	0.460770558	None	None	N
E/H	0.8832	likely_pathogenic	0.8819	pathogenic	0.056	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/I	0.8324	likely_pathogenic	0.8188	pathogenic	0.06	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/K	0.4847	ambiguous	0.4681	ambiguous	0.212	Stabilizing	0.999	D	0.628	neutral	N	0.444255223	None	None	N
E/L	0.8823	likely_pathogenic	0.8819	pathogenic	0.06	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/M	0.8646	likely_pathogenic	0.864	pathogenic	0.104	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/N	0.7151	likely_pathogenic	0.7118	pathogenic	-0.066	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/P	0.945	likely_pathogenic	0.947	pathogenic	-0.072	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/Q	0.3437	ambiguous	0.3384	benign	-0.034	Destabilizing	1.0	D	0.637	neutral	N	0.456580409	None	None	N
E/R	0.6877	likely_pathogenic	0.6849	pathogenic	0.483	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/S	0.4492	ambiguous	0.4453	ambiguous	-0.243	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
E/T	0.6134	likely_pathogenic	0.5897	pathogenic	-0.092	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/V	0.6458	likely_pathogenic	0.6346	pathogenic	-0.072	Destabilizing	1.0	D	0.727	prob.delet.	D	0.53896913	None	None	N
E/W	0.9917	likely_pathogenic	0.9922	pathogenic	-0.152	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/Y	0.9587	likely_pathogenic	0.9611	pathogenic	-0.057	Destabilizing	1.0	D	0.719	prob.delet.	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.