TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32443	97552;97553;97554	chr2:178542429;178542428;178542427	chr2:179407156;179407155;179407154
N2AB	30802	92629;92630;92631	chr2:178542429;178542428;178542427	chr2:179407156;179407155;179407154
N2A	29875	89848;89849;89850	chr2:178542429;178542428;178542427	chr2:179407156;179407155;179407154
N2B	23378	70357;70358;70359	chr2:178542429;178542428;178542427	chr2:179407156;179407155;179407154
Novex-1	23503	70732;70733;70734	chr2:178542429;178542428;178542427	chr2:179407156;179407155;179407154
Novex-2	23570	70933;70934;70935	chr2:178542429;178542428;178542427	chr2:179407156;179407155;179407154
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-124
• Domain position: 45
• Structural Position: 54
• Q(SASA): 0.7748
• 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
H/R	None	None	1.0	N	0.523	0.409	0.252681307341	gnomAD-4.0.0	2.05276E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99502E-07	0	3.31345E-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
H/A	0.6982	likely_pathogenic	0.5973	pathogenic	0.702	Stabilizing	0.999	D	0.45	neutral	None	None	None	None	N
H/C	0.4676	ambiguous	0.3598	ambiguous	0.955	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
H/D	0.6044	likely_pathogenic	0.5024	ambiguous	-0.047	Destabilizing	1.0	D	0.49	neutral	N	0.386804317	None	None	N
H/E	0.7306	likely_pathogenic	0.6177	pathogenic	-0.049	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	N
H/F	0.5106	ambiguous	0.4413	ambiguous	1.119	Stabilizing	1.0	D	0.518	neutral	None	None	None	None	N
H/G	0.6444	likely_pathogenic	0.5245	ambiguous	0.477	Stabilizing	0.999	D	0.455	neutral	None	None	None	None	N
H/I	0.7961	likely_pathogenic	0.6959	pathogenic	1.249	Stabilizing	1.0	D	0.626	neutral	None	None	None	None	N
H/K	0.6168	likely_pathogenic	0.5015	ambiguous	0.662	Stabilizing	1.0	D	0.481	neutral	None	None	None	None	N
H/L	0.3589	ambiguous	0.2575	benign	1.249	Stabilizing	1.0	D	0.592	neutral	N	0.470540421	None	None	N
H/M	0.7828	likely_pathogenic	0.7066	pathogenic	0.935	Stabilizing	1.0	D	0.559	neutral	None	None	None	None	N
H/N	0.2786	likely_benign	0.2111	benign	0.632	Stabilizing	0.999	D	0.514	neutral	N	0.433731472	None	None	N
H/P	0.6785	likely_pathogenic	0.5875	pathogenic	1.092	Stabilizing	1.0	D	0.535	neutral	N	0.444353897	None	None	N
H/Q	0.5011	ambiguous	0.3808	ambiguous	0.669	Stabilizing	1.0	D	0.535	neutral	N	0.434734337	None	None	N
H/R	0.3389	likely_benign	0.2316	benign	0.12	Stabilizing	1.0	D	0.523	neutral	N	0.421631753	None	None	N
H/S	0.5146	ambiguous	0.4195	ambiguous	0.804	Stabilizing	1.0	D	0.483	neutral	None	None	None	None	N
H/T	0.6715	likely_pathogenic	0.5621	ambiguous	0.892	Stabilizing	1.0	D	0.54	neutral	None	None	None	None	N
H/V	0.7152	likely_pathogenic	0.5893	pathogenic	1.092	Stabilizing	1.0	D	0.609	neutral	None	None	None	None	N
H/W	0.6238	likely_pathogenic	0.5418	ambiguous	0.959	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	N
H/Y	0.2482	likely_benign	0.1834	benign	1.297	Stabilizing	0.999	D	0.457	neutral	N	0.493435924	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.