TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15596	47011;47012;47013	chr2:178618764;178618763;178618762	chr2:179483491;179483490;179483489
N2AB	13955	42088;42089;42090	chr2:178618764;178618763;178618762	chr2:179483491;179483490;179483489
N2A	13028	39307;39308;39309	chr2:178618764;178618763;178618762	chr2:179483491;179483490;179483489
N2B	6531	19816;19817;19818	chr2:178618764;178618763;178618762	chr2:179483491;179483490;179483489
Novex-1	6656	20191;20192;20193	chr2:178618764;178618763;178618762	chr2:179483491;179483490;179483489
Novex-2	6723	20392;20393;20394	chr2:178618764;178618763;178618762	chr2:179483491;179483490;179483489
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-108
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.3978
• 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/N	rs1576521599	None	0.801	N	0.371	0.19	0.267755039894	gnomAD-4.0.0	1.59587E-06	None	None	None	None	N	None	0	0	None	4.78103E-05	0	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
K/A	0.1909	likely_benign	0.2793	benign	-0.43	Destabilizing	0.688	D	0.382	neutral	None	None	None	None	N
K/C	0.5865	likely_pathogenic	0.7539	pathogenic	-0.302	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	N
K/D	0.4645	ambiguous	0.5801	pathogenic	0.052	Stabilizing	0.842	D	0.447	neutral	None	None	None	None	N
K/E	0.1347	likely_benign	0.1877	benign	0.138	Stabilizing	0.454	N	0.335	neutral	N	0.507241194	None	None	N
K/F	0.5525	ambiguous	0.7032	pathogenic	-0.205	Destabilizing	0.949	D	0.489	neutral	None	None	None	None	N
K/G	0.3531	ambiguous	0.4878	ambiguous	-0.771	Destabilizing	0.915	D	0.457	neutral	None	None	None	None	N
K/H	0.2772	likely_benign	0.3837	ambiguous	-1.174	Destabilizing	0.974	D	0.433	neutral	None	None	None	None	N
K/I	0.2183	likely_benign	0.2901	benign	0.434	Stabilizing	0.876	D	0.472	neutral	N	0.515132949	None	None	N
K/L	0.2099	likely_benign	0.3121	benign	0.434	Stabilizing	0.016	N	0.229	neutral	None	None	None	None	N
K/M	0.1761	likely_benign	0.2529	benign	0.316	Stabilizing	0.949	D	0.441	neutral	None	None	None	None	N
K/N	0.3308	likely_benign	0.4306	ambiguous	-0.163	Destabilizing	0.801	D	0.371	neutral	N	0.512818854	None	None	N
K/P	0.2997	likely_benign	0.3976	ambiguous	0.177	Stabilizing	0.016	N	0.267	neutral	None	None	None	None	N
K/Q	0.1187	likely_benign	0.1577	benign	-0.244	Destabilizing	0.136	N	0.184	neutral	N	0.500593532	None	None	N
K/R	0.0732	likely_benign	0.0892	benign	-0.507	Destabilizing	0.012	N	0.198	neutral	N	0.471639029	None	None	N
K/S	0.3018	likely_benign	0.412	ambiguous	-0.776	Destabilizing	0.842	D	0.279	neutral	None	None	None	None	N
K/T	0.1484	likely_benign	0.1997	benign	-0.493	Destabilizing	0.891	D	0.397	neutral	N	0.510168819	None	None	N
K/V	0.1897	likely_benign	0.263	benign	0.177	Stabilizing	0.728	D	0.461	neutral	None	None	None	None	N
K/W	0.6223	likely_pathogenic	0.7825	pathogenic	-0.109	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
K/Y	0.4688	ambiguous	0.6167	pathogenic	0.177	Stabilizing	0.991	D	0.487	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.