TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27745	83458;83459;83460	chr2:178562899;178562898;178562897	chr2:179427626;179427625;179427624
N2AB	26104	78535;78536;78537	chr2:178562899;178562898;178562897	chr2:179427626;179427625;179427624
N2A	25177	75754;75755;75756	chr2:178562899;178562898;178562897	chr2:179427626;179427625;179427624
N2B	18680	56263;56264;56265	chr2:178562899;178562898;178562897	chr2:179427626;179427625;179427624
Novex-1	18805	56638;56639;56640	chr2:178562899;178562898;178562897	chr2:179427626;179427625;179427624
Novex-2	18872	56839;56840;56841	chr2:178562899;178562898;178562897	chr2:179427626;179427625;179427624
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-141
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.2823
• 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
N/S	None	None	0.028	N	0.172	0.092	0.0611884634855	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02737E-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
N/A	0.2759	likely_benign	0.2674	benign	-1.326	Destabilizing	0.373	N	0.541	neutral	None	None	None	None	N
N/C	0.2178	likely_benign	0.2133	benign	-0.665	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	N
N/D	0.2625	likely_benign	0.2587	benign	-1.772	Destabilizing	0.684	D	0.5	neutral	N	0.412860341	None	None	N
N/E	0.5201	ambiguous	0.5358	ambiguous	-1.554	Destabilizing	0.742	D	0.484	neutral	None	None	None	None	N
N/F	0.4998	ambiguous	0.5071	ambiguous	-0.798	Destabilizing	0.953	D	0.641	neutral	None	None	None	None	N
N/G	0.4486	ambiguous	0.4437	ambiguous	-1.713	Destabilizing	0.373	N	0.487	neutral	None	None	None	None	N
N/H	0.0902	likely_benign	0.0892	benign	-1.143	Destabilizing	0.979	D	0.511	neutral	N	0.442316457	None	None	N
N/I	0.1501	likely_benign	0.1522	benign	-0.294	Destabilizing	0.521	D	0.571	neutral	N	0.362354163	None	None	N
N/K	0.3938	ambiguous	0.403	ambiguous	-0.409	Destabilizing	0.684	D	0.485	neutral	N	0.385884384	None	None	N
N/L	0.1957	likely_benign	0.2005	benign	-0.294	Destabilizing	0.373	N	0.531	neutral	None	None	None	None	N
N/M	0.2976	likely_benign	0.2968	benign	-0.102	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	N
N/P	0.9458	likely_pathogenic	0.9467	pathogenic	-0.612	Destabilizing	0.953	D	0.6	neutral	None	None	None	None	N
N/Q	0.3649	ambiguous	0.3634	ambiguous	-1.026	Destabilizing	0.91	D	0.499	neutral	None	None	None	None	N
N/R	0.3956	ambiguous	0.4041	ambiguous	-0.502	Destabilizing	0.91	D	0.501	neutral	None	None	None	None	N
N/S	0.0926	likely_benign	0.0897	benign	-1.34	Destabilizing	0.028	N	0.172	neutral	N	0.383748156	None	None	N
N/T	0.1146	likely_benign	0.1102	benign	-0.937	Destabilizing	0.028	N	0.156	neutral	N	0.301705562	None	None	N
N/V	0.1649	likely_benign	0.1654	benign	-0.612	Destabilizing	0.016	N	0.424	neutral	None	None	None	None	N
N/W	0.8115	likely_pathogenic	0.8134	pathogenic	-0.614	Destabilizing	0.996	D	0.686	prob.neutral	None	None	None	None	N
N/Y	0.1704	likely_benign	0.174	benign	-0.32	Destabilizing	0.979	D	0.603	neutral	N	0.460035426	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.