TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26434	79525;79526;79527	chr2:178566832;178566831;178566830	chr2:179431559;179431558;179431557
N2AB	24793	74602;74603;74604	chr2:178566832;178566831;178566830	chr2:179431559;179431558;179431557
N2A	23866	71821;71822;71823	chr2:178566832;178566831;178566830	chr2:179431559;179431558;179431557
N2B	17369	52330;52331;52332	chr2:178566832;178566831;178566830	chr2:179431559;179431558;179431557
Novex-1	17494	52705;52706;52707	chr2:178566832;178566831;178566830	chr2:179431559;179431558;179431557
Novex-2	17561	52906;52907;52908	chr2:178566832;178566831;178566830	chr2:179431559;179431558;179431557
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-80
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4488
• 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
I/T	None	None	None	N	0.181	0.156	0.536661227952	gnomAD-4.0.0	3.18402E-06	None	None	None	None	I	None	0	0	None	0	2.77809E-05	None	0	0	2.85889E-06	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
I/A	0.5268	ambiguous	0.4812	ambiguous	-1.27	Destabilizing	0.025	N	0.249	neutral	None	None	None	None	I
I/C	0.7512	likely_pathogenic	0.6979	pathogenic	-0.722	Destabilizing	0.667	D	0.311	neutral	None	None	None	None	I
I/D	0.9456	likely_pathogenic	0.9497	pathogenic	-0.848	Destabilizing	0.22	N	0.343	neutral	None	None	None	None	I
I/E	0.8647	likely_pathogenic	0.884	pathogenic	-0.87	Destabilizing	0.22	N	0.299	neutral	None	None	None	None	I
I/F	0.3017	likely_benign	0.2895	benign	-0.873	Destabilizing	0.22	N	0.277	neutral	None	None	None	None	I
I/G	0.7536	likely_pathogenic	0.7176	pathogenic	-1.541	Destabilizing	0.22	N	0.308	neutral	None	None	None	None	I
I/H	0.7286	likely_pathogenic	0.7493	pathogenic	-0.676	Destabilizing	0.958	D	0.32	neutral	None	None	None	None	I
I/K	0.7833	likely_pathogenic	0.8145	pathogenic	-0.91	Destabilizing	0.175	N	0.293	neutral	N	0.456640909	None	None	I
I/L	0.1559	likely_benign	0.156	benign	-0.621	Destabilizing	0.008	N	0.164	neutral	N	0.476440178	None	None	I
I/M	0.1079	likely_benign	0.0927	benign	-0.533	Destabilizing	0.427	N	0.328	neutral	N	0.477018968	None	None	I
I/N	0.3846	ambiguous	0.3804	ambiguous	-0.724	Destabilizing	0.22	N	0.337	neutral	None	None	None	None	I
I/P	0.966	likely_pathogenic	0.9705	pathogenic	-0.806	Destabilizing	0.364	N	0.376	neutral	None	None	None	None	I
I/Q	0.6188	likely_pathogenic	0.6426	pathogenic	-0.918	Destabilizing	0.667	D	0.363	neutral	None	None	None	None	I
I/R	0.7348	likely_pathogenic	0.7704	pathogenic	-0.268	Destabilizing	0.602	D	0.379	neutral	N	0.467820695	None	None	I
I/S	0.4247	ambiguous	0.402	ambiguous	-1.234	Destabilizing	0.055	N	0.281	neutral	None	None	None	None	I
I/T	0.2393	likely_benign	0.2268	benign	-1.149	Destabilizing	None	N	0.181	neutral	N	0.38216458	None	None	I
I/V	0.1	likely_benign	0.084	benign	-0.806	Destabilizing	None	N	0.126	neutral	N	0.387031682	None	None	I
I/W	0.8831	likely_pathogenic	0.892	pathogenic	-0.931	Destabilizing	0.958	D	0.349	neutral	None	None	None	None	I
I/Y	0.6628	likely_pathogenic	0.6898	pathogenic	-0.718	Destabilizing	0.667	D	0.349	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.