TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19380	58363;58364;58365	chr2:178594356;178594355;178594354	chr2:179459083;179459082;179459081
N2AB	17739	53440;53441;53442	chr2:178594356;178594355;178594354	chr2:179459083;179459082;179459081
N2A	16812	50659;50660;50661	chr2:178594356;178594355;178594354	chr2:179459083;179459082;179459081
N2B	10315	31168;31169;31170	chr2:178594356;178594355;178594354	chr2:179459083;179459082;179459081
Novex-1	10440	31543;31544;31545	chr2:178594356;178594355;178594354	chr2:179459083;179459082;179459081
Novex-2	10507	31744;31745;31746	chr2:178594356;178594355;178594354	chr2:179459083;179459082;179459081
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-28
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.5156
• 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
K/T	rs1245279855	-0.11	0.883	N	0.502	0.202	0.260249123532	gnomAD-2.1.1	4.3E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.83E-05	None	0	0	0
K/T	rs1245279855	-0.11	0.883	N	0.502	0.202	0.260249123532	gnomAD-4.0.0	1.64569E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.52064E-05	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
K/A	0.7814	likely_pathogenic	0.7458	pathogenic	-0.173	Destabilizing	0.74	D	0.514	neutral	None	None	None	None	N
K/C	0.8344	likely_pathogenic	0.8437	pathogenic	-0.122	Destabilizing	0.996	D	0.756	deleterious	None	None	None	None	N
K/D	0.9578	likely_pathogenic	0.9438	pathogenic	-0.089	Destabilizing	0.953	D	0.531	neutral	None	None	None	None	N
K/E	0.5339	ambiguous	0.4865	ambiguous	-0.056	Destabilizing	0.682	D	0.515	neutral	N	0.514702204	None	None	N
K/F	0.9463	likely_pathogenic	0.9334	pathogenic	-0.214	Destabilizing	0.996	D	0.699	prob.delet.	None	None	None	None	N
K/G	0.8979	likely_pathogenic	0.8714	pathogenic	-0.454	Destabilizing	0.909	D	0.427	neutral	None	None	None	None	N
K/H	0.5357	ambiguous	0.5251	ambiguous	-0.926	Destabilizing	0.987	D	0.506	neutral	None	None	None	None	N
K/I	0.6011	likely_pathogenic	0.5535	ambiguous	0.51	Stabilizing	0.953	D	0.76	deleterious	None	None	None	None	N
K/L	0.7038	likely_pathogenic	0.6692	pathogenic	0.51	Stabilizing	0.909	D	0.427	neutral	None	None	None	None	N
K/M	0.5219	ambiguous	0.4888	ambiguous	0.522	Stabilizing	0.994	D	0.503	neutral	N	0.473540696	None	None	N
K/N	0.8911	likely_pathogenic	0.859	pathogenic	0.09	Stabilizing	0.883	D	0.568	neutral	N	0.503001257	None	None	N
K/P	0.9907	likely_pathogenic	0.9887	pathogenic	0.313	Stabilizing	0.984	D	0.516	neutral	None	None	None	None	N
K/Q	0.2438	likely_benign	0.2321	benign	-0.128	Destabilizing	0.883	D	0.603	neutral	N	0.506026793	None	None	N
K/R	0.0861	likely_benign	0.0847	benign	-0.246	Destabilizing	0.007	N	0.233	neutral	N	0.459563784	None	None	N
K/S	0.8568	likely_pathogenic	0.8208	pathogenic	-0.453	Destabilizing	0.74	D	0.58	neutral	None	None	None	None	N
K/T	0.4828	ambiguous	0.4358	ambiguous	-0.251	Destabilizing	0.883	D	0.502	neutral	N	0.466032278	None	None	N
K/V	0.5428	ambiguous	0.5044	ambiguous	0.313	Stabilizing	0.953	D	0.682	prob.neutral	None	None	None	None	N
K/W	0.9244	likely_pathogenic	0.9124	pathogenic	-0.144	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
K/Y	0.8917	likely_pathogenic	0.8762	pathogenic	0.189	Stabilizing	0.984	D	0.669	prob.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.