TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27593	83002;83003;83004	chr2:178563355;178563354;178563353	chr2:179428082;179428081;179428080
N2AB	25952	78079;78080;78081	chr2:178563355;178563354;178563353	chr2:179428082;179428081;179428080
N2A	25025	75298;75299;75300	chr2:178563355;178563354;178563353	chr2:179428082;179428081;179428080
N2B	18528	55807;55808;55809	chr2:178563355;178563354;178563353	chr2:179428082;179428081;179428080
Novex-1	18653	56182;56183;56184	chr2:178563355;178563354;178563353	chr2:179428082;179428081;179428080
Novex-2	18720	56383;56384;56385	chr2:178563355;178563354;178563353	chr2:179428082;179428081;179428080
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: Fn3-89
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.7947
• 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/Q	None	None	0.901	N	0.595	0.231	0.262662153117	gnomAD-4.0.0	3.18321E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71729E-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
K/A	0.5296	ambiguous	0.5149	ambiguous	-0.47	Destabilizing	0.775	D	0.595	neutral	None	None	None	None	N
K/C	0.8166	likely_pathogenic	0.8177	pathogenic	-0.496	Destabilizing	0.996	D	0.741	deleterious	None	None	None	None	N
K/D	0.8542	likely_pathogenic	0.8477	pathogenic	0.046	Stabilizing	0.961	D	0.653	neutral	None	None	None	None	N
K/E	0.4622	ambiguous	0.4395	ambiguous	0.148	Stabilizing	0.722	D	0.591	neutral	N	0.493313785	None	None	N
K/F	0.9046	likely_pathogenic	0.9062	pathogenic	-0.289	Destabilizing	0.987	D	0.717	prob.delet.	None	None	None	None	N
K/G	0.697	likely_pathogenic	0.6968	pathogenic	-0.804	Destabilizing	0.775	D	0.619	neutral	None	None	None	None	N
K/H	0.4803	ambiguous	0.4709	ambiguous	-1.09	Destabilizing	0.961	D	0.697	prob.neutral	None	None	None	None	N
K/I	0.6136	likely_pathogenic	0.5764	pathogenic	0.377	Stabilizing	0.961	D	0.717	prob.delet.	None	None	None	None	N
K/L	0.5559	ambiguous	0.5321	ambiguous	0.377	Stabilizing	0.775	D	0.619	neutral	None	None	None	None	N
K/M	0.4708	ambiguous	0.4419	ambiguous	0.151	Stabilizing	0.995	D	0.683	prob.neutral	N	0.487119636	None	None	N
K/N	0.7613	likely_pathogenic	0.7459	pathogenic	-0.26	Destabilizing	0.901	D	0.579	neutral	N	0.481586228	None	None	N
K/P	0.521	ambiguous	0.5313	ambiguous	0.125	Stabilizing	0.987	D	0.69	prob.neutral	None	None	None	None	N
K/Q	0.2298	likely_benign	0.2281	benign	-0.287	Destabilizing	0.901	D	0.595	neutral	N	0.518326873	None	None	N
K/R	0.0947	likely_benign	0.0976	benign	-0.415	Destabilizing	0.003	N	0.232	neutral	N	0.478480406	None	None	N
K/S	0.6488	likely_pathogenic	0.6433	pathogenic	-0.885	Destabilizing	0.775	D	0.569	neutral	None	None	None	None	N
K/T	0.3961	ambiguous	0.3731	ambiguous	-0.573	Destabilizing	0.722	D	0.623	neutral	N	0.480825759	None	None	N
K/V	0.5337	ambiguous	0.5077	ambiguous	0.125	Stabilizing	0.961	D	0.649	neutral	None	None	None	None	N
K/W	0.8809	likely_pathogenic	0.8928	pathogenic	-0.206	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
K/Y	0.805	likely_pathogenic	0.8015	pathogenic	0.096	Stabilizing	0.987	D	0.727	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.