TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8024	24295;24296;24297	chr2:178719320;178719319;178719318	chr2:179584047;179584046;179584045
N2AB	7707	23344;23345;23346	chr2:178719320;178719319;178719318	chr2:179584047;179584046;179584045
N2A	6780	20563;20564;20565	chr2:178719320;178719319;178719318	chr2:179584047;179584046;179584045
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-65
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.5498
• 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/Q	None	None	0.939	N	0.548	0.216	0.28722502521	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	6.56251E-06	0	3.66327E-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
E/A	0.1413	likely_benign	0.157	benign	-0.589	Destabilizing	0.939	D	0.581	neutral	N	0.487302626	None	None	N
E/C	0.7915	likely_pathogenic	0.829	pathogenic	-0.387	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
E/D	0.1752	likely_benign	0.2094	benign	-0.497	Destabilizing	0.939	D	0.503	neutral	N	0.489820613	None	None	N
E/F	0.6911	likely_pathogenic	0.7294	pathogenic	-0.089	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
E/G	0.1613	likely_benign	0.1834	benign	-0.844	Destabilizing	0.982	D	0.553	neutral	N	0.512448	None	None	N
E/H	0.3399	likely_benign	0.4016	ambiguous	0.222	Stabilizing	0.999	D	0.615	neutral	None	None	None	None	N
E/I	0.2984	likely_benign	0.3283	benign	0.077	Stabilizing	0.993	D	0.696	prob.neutral	None	None	None	None	N
E/K	0.0744	likely_benign	0.0842	benign	0.095	Stabilizing	0.046	N	0.253	neutral	N	0.517396658	None	None	N
E/L	0.3149	likely_benign	0.3488	ambiguous	0.077	Stabilizing	0.986	D	0.628	neutral	None	None	None	None	N
E/M	0.3452	ambiguous	0.372	ambiguous	0.092	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	N
E/N	0.2518	likely_benign	0.3077	benign	-0.518	Destabilizing	0.986	D	0.616	neutral	None	None	None	None	N
E/P	0.3063	likely_benign	0.357	ambiguous	-0.125	Destabilizing	0.993	D	0.675	neutral	None	None	None	None	N
E/Q	0.104	likely_benign	0.114	benign	-0.422	Destabilizing	0.939	D	0.548	neutral	N	0.519071527	None	None	N
E/R	0.1346	likely_benign	0.1504	benign	0.478	Stabilizing	0.91	D	0.587	neutral	None	None	None	None	N
E/S	0.1948	likely_benign	0.2291	benign	-0.668	Destabilizing	0.953	D	0.577	neutral	None	None	None	None	N
E/T	0.2031	likely_benign	0.235	benign	-0.445	Destabilizing	0.986	D	0.609	neutral	None	None	None	None	N
E/V	0.1894	likely_benign	0.2043	benign	-0.125	Destabilizing	0.991	D	0.611	neutral	D	0.533944978	None	None	N
E/W	0.8333	likely_pathogenic	0.864	pathogenic	0.193	Stabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/Y	0.4982	ambiguous	0.5661	pathogenic	0.18	Stabilizing	0.998	D	0.652	neutral	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.