TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15900	47923;47924;47925	chr2:178617387;178617386;178617385	chr2:179482114;179482113;179482112
N2AB	14259	43000;43001;43002	chr2:178617387;178617386;178617385	chr2:179482114;179482113;179482112
N2A	13332	40219;40220;40221	chr2:178617387;178617386;178617385	chr2:179482114;179482113;179482112
N2B	6835	20728;20729;20730	chr2:178617387;178617386;178617385	chr2:179482114;179482113;179482112
Novex-1	6960	21103;21104;21105	chr2:178617387;178617386;178617385	chr2:179482114;179482113;179482112
Novex-2	7027	21304;21305;21306	chr2:178617387;178617386;178617385	chr2:179482114;179482113;179482112
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-3
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2838
• 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/A	None	None	0.999	N	0.661	0.48	0.493494165309	gnomAD-4.0.0	1.65614E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.56304E-05	0
E/K	rs772625773	-0.829	1.0	N	0.577	0.428	0.442363741745	gnomAD-2.1.1	3.68E-05	None	None	None	None	N	None	7.24E-05	0	None	0	0	None	8.18E-05	None	0	5.04E-05	0
E/K	rs772625773	-0.829	1.0	N	0.577	0.428	0.442363741745	gnomAD-4.0.0	1.94871E-05	None	None	None	None	N	None	3.0954E-05	0	None	0	2.55872E-05	None	0	0	2.0862E-05	2.48614E-05	1.68327E-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	0.1649	likely_benign	0.1633	benign	-0.957	Destabilizing	0.999	D	0.661	neutral	N	0.482624527	None	None	N
E/C	0.8423	likely_pathogenic	0.8278	pathogenic	-0.621	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/D	0.2378	likely_benign	0.2723	benign	-1.339	Destabilizing	0.999	D	0.417	neutral	N	0.484316251	None	None	N
E/F	0.7968	likely_pathogenic	0.7932	pathogenic	-0.346	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/G	0.2526	likely_benign	0.2339	benign	-1.354	Destabilizing	1.0	D	0.677	prob.neutral	N	0.499231432	None	None	N
E/H	0.5254	ambiguous	0.5232	ambiguous	-0.737	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
E/I	0.2931	likely_benign	0.3145	benign	0.141	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/K	0.1208	likely_benign	0.1101	benign	-1.059	Destabilizing	1.0	D	0.577	neutral	N	0.475403595	None	None	N
E/L	0.332	likely_benign	0.341	ambiguous	0.141	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/M	0.4123	ambiguous	0.4199	ambiguous	0.675	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	N
E/N	0.367	ambiguous	0.3974	ambiguous	-1.476	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/P	0.3643	ambiguous	0.3522	ambiguous	-0.204	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/Q	0.1376	likely_benign	0.1315	benign	-1.302	Destabilizing	1.0	D	0.611	neutral	N	0.465092452	None	None	N
E/R	0.2175	likely_benign	0.1871	benign	-0.761	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
E/S	0.2826	likely_benign	0.2889	benign	-1.847	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/T	0.2618	likely_benign	0.2688	benign	-1.521	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/V	0.1817	likely_benign	0.1898	benign	-0.204	Destabilizing	1.0	D	0.743	deleterious	N	0.473803168	None	None	N
E/W	0.9027	likely_pathogenic	0.8944	pathogenic	-0.141	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/Y	0.7252	likely_pathogenic	0.7211	pathogenic	-0.13	Destabilizing	1.0	D	0.695	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.