TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1303	4132;4133;4134	chr2:178779285;178779284;178779283	chr2:179644012;179644011;179644010
N2AB	1303	4132;4133;4134	chr2:178779285;178779284;178779283	chr2:179644012;179644011;179644010
N2A	1303	4132;4133;4134	chr2:178779285;178779284;178779283	chr2:179644012;179644011;179644010
N2B	1257	3994;3995;3996	chr2:178779285;178779284;178779283	chr2:179644012;179644011;179644010
Novex-1	1257	3994;3995;3996	chr2:178779285;178779284;178779283	chr2:179644012;179644011;179644010
Novex-2	1257	3994;3995;3996	chr2:178779285;178779284;178779283	chr2:179644012;179644011;179644010
Novex-3	1303	4132;4133;4134	chr2:178779285;178779284;178779283	chr2:179644012;179644011;179644010

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-5
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.7882
• Predicted PPI site: I

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
L/I	None	None	0.033	N	0.405	0.054	0.421920138742	gnomAD-4.0.0	1.36846E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73491E-04	0	0	1.65612E-05
L/P	rs1407839718	-0.327	0.912	N	0.483	0.576	0.813802140646	gnomAD-2.1.1	4E-06	None	None	None	None	I	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
L/P	rs1407839718	-0.327	0.912	N	0.483	0.576	0.813802140646	gnomAD-4.0.0	1.36846E-06	None	None	None	None	I	None	0	0	None	0	5.04414E-05	None	0	0	0	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
L/A	0.2355	likely_benign	0.2732	benign	-0.894	Destabilizing	0.241	N	0.415	neutral	None	None	None	None	I
L/C	0.7057	likely_pathogenic	0.7334	pathogenic	-0.672	Destabilizing	0.944	D	0.439	neutral	None	None	None	None	I
L/D	0.7986	likely_pathogenic	0.85	pathogenic	-0.397	Destabilizing	0.818	D	0.482	neutral	None	None	None	None	I
L/E	0.4503	ambiguous	0.5206	ambiguous	-0.454	Destabilizing	0.818	D	0.495	neutral	None	None	None	None	I
L/F	0.1626	likely_benign	0.1935	benign	-0.672	Destabilizing	0.001	N	0.289	neutral	N	0.490476701	None	None	I
L/G	0.5676	likely_pathogenic	0.6405	pathogenic	-1.117	Destabilizing	0.818	D	0.481	neutral	None	None	None	None	I
L/H	0.3077	likely_benign	0.3757	ambiguous	-0.294	Destabilizing	0.975	D	0.479	neutral	N	0.510569004	None	None	I
L/I	0.1186	likely_benign	0.1321	benign	-0.406	Destabilizing	0.033	N	0.405	neutral	N	0.474196928	None	None	I
L/K	0.3072	likely_benign	0.3605	ambiguous	-0.591	Destabilizing	0.818	D	0.483	neutral	None	None	None	None	I
L/M	0.1151	likely_benign	0.1274	benign	-0.446	Destabilizing	0.024	N	0.284	neutral	None	None	None	None	I
L/N	0.4968	ambiguous	0.5811	pathogenic	-0.401	Destabilizing	0.932	D	0.483	neutral	None	None	None	None	I
L/P	0.3275	likely_benign	0.4065	ambiguous	-0.536	Destabilizing	0.912	D	0.483	neutral	N	0.485538884	None	None	I
L/Q	0.1681	likely_benign	0.2064	benign	-0.604	Destabilizing	0.818	D	0.488	neutral	None	None	None	None	I
L/R	0.2134	likely_benign	0.2552	benign	0.001	Stabilizing	0.773	D	0.493	neutral	N	0.482197364	None	None	I
L/S	0.2959	likely_benign	0.3526	ambiguous	-0.895	Destabilizing	0.69	D	0.478	neutral	None	None	None	None	I
L/T	0.2049	likely_benign	0.2469	benign	-0.84	Destabilizing	0.388	N	0.454	neutral	None	None	None	None	I
L/V	0.1077	likely_benign	0.1242	benign	-0.536	Destabilizing	0.001	N	0.263	neutral	N	0.421744186	None	None	I
L/W	0.3101	likely_benign	0.3775	ambiguous	-0.698	Destabilizing	0.981	D	0.497	neutral	None	None	None	None	I
L/Y	0.4449	ambiguous	0.5237	ambiguous	-0.47	Destabilizing	0.527	D	0.431	neutral	None	None	None	None	I

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.