TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19078	57457;57458;57459	chr2:178597938;178597937;178597936	chr2:179462665;179462664;179462663
N2AB	17437	52534;52535;52536	chr2:178597938;178597937;178597936	chr2:179462665;179462664;179462663
N2A	16510	49753;49754;49755	chr2:178597938;178597937;178597936	chr2:179462665;179462664;179462663
N2B	10013	30262;30263;30264	chr2:178597938;178597937;178597936	chr2:179462665;179462664;179462663
Novex-1	10138	30637;30638;30639	chr2:178597938;178597937;178597936	chr2:179462665;179462664;179462663
Novex-2	10205	30838;30839;30840	chr2:178597938;178597937;178597936	chr2:179462665;179462664;179462663
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-26
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.1422
• 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
T/I	rs1452086800	0.455	0.294	N	0.68	0.196	0.324986149311	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/I	rs1452086800	0.455	0.294	N	0.68	0.196	0.324986149311	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4334E-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
T/A	0.0701	likely_benign	0.0677	benign	-0.159	Destabilizing	0.005	N	0.235	neutral	N	0.428048799	None	None	N
T/C	0.3606	ambiguous	0.3886	ambiguous	-0.519	Destabilizing	0.989	D	0.644	neutral	None	None	None	None	N
T/D	0.2996	likely_benign	0.2786	benign	-0.224	Destabilizing	0.524	D	0.682	prob.neutral	None	None	None	None	N
T/E	0.2526	likely_benign	0.2225	benign	-0.317	Destabilizing	0.355	N	0.676	prob.neutral	None	None	None	None	N
T/F	0.3039	likely_benign	0.3023	benign	-0.849	Destabilizing	0.794	D	0.676	prob.neutral	None	None	None	None	N
T/G	0.167	likely_benign	0.1663	benign	-0.188	Destabilizing	0.185	N	0.597	neutral	None	None	None	None	N
T/H	0.2692	likely_benign	0.2474	benign	-0.273	Destabilizing	0.96	D	0.637	neutral	None	None	None	None	N
T/I	0.1933	likely_benign	0.1725	benign	-0.196	Destabilizing	0.294	N	0.68	prob.neutral	N	0.490769339	None	None	N
T/K	0.1851	likely_benign	0.1473	benign	-0.403	Destabilizing	0.003	N	0.45	neutral	N	0.495620585	None	None	N
T/L	0.1066	likely_benign	0.1014	benign	-0.196	Destabilizing	0.003	N	0.425	neutral	None	None	None	None	N
T/M	0.0945	likely_benign	0.0967	benign	-0.3	Destabilizing	0.794	D	0.657	prob.neutral	None	None	None	None	N
T/N	0.1105	likely_benign	0.1022	benign	-0.223	Destabilizing	0.524	D	0.633	neutral	None	None	None	None	N
T/P	0.0781	likely_benign	0.0676	benign	-0.163	Destabilizing	0.627	D	0.772	deleterious	N	0.486001024	None	None	N
T/Q	0.2033	likely_benign	0.1797	benign	-0.416	Destabilizing	0.794	D	0.781	deleterious	None	None	None	None	N
T/R	0.1876	likely_benign	0.1524	benign	-0.098	Destabilizing	0.294	N	0.723	deleterious	N	0.473820639	None	None	N
T/S	0.0929	likely_benign	0.0912	benign	-0.364	Destabilizing	0.013	N	0.332	neutral	N	0.409308322	None	None	N
T/V	0.1435	likely_benign	0.1365	benign	-0.163	Destabilizing	0.185	N	0.507	neutral	None	None	None	None	N
T/W	0.6112	likely_pathogenic	0.6231	pathogenic	-0.964	Destabilizing	0.989	D	0.67	prob.neutral	None	None	None	None	N
T/Y	0.3389	likely_benign	0.329	benign	-0.645	Destabilizing	0.96	D	0.662	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.