TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32415	97468;97469;97470	chr2:178542513;178542512;178542511	chr2:179407240;179407239;179407238
N2AB	30774	92545;92546;92547	chr2:178542513;178542512;178542511	chr2:179407240;179407239;179407238
N2A	29847	89764;89765;89766	chr2:178542513;178542512;178542511	chr2:179407240;179407239;179407238
N2B	23350	70273;70274;70275	chr2:178542513;178542512;178542511	chr2:179407240;179407239;179407238
Novex-1	23475	70648;70649;70650	chr2:178542513;178542512;178542511	chr2:179407240;179407239;179407238
Novex-2	23542	70849;70850;70851	chr2:178542513;178542512;178542511	chr2:179407240;179407239;179407238
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: Fn3-124
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.3968
• 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	rs768529940	-0.323	0.007	N	0.263	0.274	0.401753679984	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	1.40964E-04
T/I	rs768529940	-0.323	0.007	N	0.263	0.274	0.401753679984	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.1425E-04	0
T/I	rs768529940	-0.323	0.007	N	0.263	0.274	0.401753679984	gnomAD-4.0.0	7.44529E-06	None	None	None	None	N	None	1.33561E-05	0	None	0	0	None	0	0	0	1.09825E-04	1.60298E-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
T/A	0.074	likely_benign	0.0677	benign	-0.642	Destabilizing	0.101	N	0.294	neutral	N	0.52191147	None	None	N
T/C	0.3435	ambiguous	0.2768	benign	-0.436	Destabilizing	0.983	D	0.359	neutral	None	None	None	None	N
T/D	0.2972	likely_benign	0.2655	benign	-0.821	Destabilizing	0.264	N	0.386	neutral	None	None	None	None	N
T/E	0.2791	likely_benign	0.2601	benign	-0.867	Destabilizing	0.418	N	0.385	neutral	None	None	None	None	N
T/F	0.2634	likely_benign	0.1972	benign	-1.153	Destabilizing	0.836	D	0.447	neutral	None	None	None	None	N
T/G	0.1768	likely_benign	0.1467	benign	-0.803	Destabilizing	0.129	N	0.339	neutral	None	None	None	None	N
T/H	0.2354	likely_benign	0.1989	benign	-1.248	Destabilizing	0.716	D	0.387	neutral	None	None	None	None	N
T/I	0.2274	likely_benign	0.1808	benign	-0.317	Destabilizing	0.007	N	0.263	neutral	N	0.516347296	None	None	N
T/K	0.2778	likely_benign	0.2391	benign	-0.533	Destabilizing	0.213	N	0.386	neutral	N	0.473199799	None	None	N
T/L	0.1187	likely_benign	0.0954	benign	-0.317	Destabilizing	0.129	N	0.356	neutral	None	None	None	None	N
T/M	0.1015	likely_benign	0.0903	benign	0.237	Stabilizing	0.061	N	0.337	neutral	None	None	None	None	N
T/N	0.0905	likely_benign	0.0785	benign	-0.517	Destabilizing	0.001	N	0.069	neutral	None	None	None	None	N
T/P	0.5274	ambiguous	0.3973	ambiguous	-0.397	Destabilizing	0.794	D	0.435	neutral	N	0.505497969	None	None	N
T/Q	0.2222	likely_benign	0.1935	benign	-0.898	Destabilizing	0.716	D	0.43	neutral	None	None	None	None	N
T/R	0.2505	likely_benign	0.2003	benign	-0.171	Destabilizing	0.655	D	0.445	neutral	N	0.510443682	None	None	N
T/S	0.078	likely_benign	0.071	benign	-0.664	Destabilizing	0.007	N	0.157	neutral	N	0.45512633	None	None	N
T/V	0.1584	likely_benign	0.1249	benign	-0.397	Destabilizing	0.01	N	0.109	neutral	None	None	None	None	N
T/W	0.656	likely_pathogenic	0.5583	ambiguous	-1.106	Destabilizing	0.983	D	0.408	neutral	None	None	None	None	N
T/Y	0.267	likely_benign	0.2199	benign	-0.802	Destabilizing	0.94	D	0.417	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.