TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27485	82678;82679;82680	chr2:178563679;178563678;178563677	chr2:179428406;179428405;179428404
N2AB	25844	77755;77756;77757	chr2:178563679;178563678;178563677	chr2:179428406;179428405;179428404
N2A	24917	74974;74975;74976	chr2:178563679;178563678;178563677	chr2:179428406;179428405;179428404
N2B	18420	55483;55484;55485	chr2:178563679;178563678;178563677	chr2:179428406;179428405;179428404
Novex-1	18545	55858;55859;55860	chr2:178563679;178563678;178563677	chr2:179428406;179428405;179428404
Novex-2	18612	56059;56060;56061	chr2:178563679;178563678;178563677	chr2:179428406;179428405;179428404
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-88
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1421
• 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
S/Y	None	None	0.99	N	0.759	0.463	0.738581242654	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.1731	likely_benign	0.1296	benign	-0.445	Destabilizing	0.014	N	0.223	neutral	N	0.498852152	None	None	N
S/C	0.1687	likely_benign	0.1417	benign	-0.756	Destabilizing	0.992	D	0.698	prob.neutral	N	0.506805097	None	None	N
S/D	0.9285	likely_pathogenic	0.897	pathogenic	-1.819	Destabilizing	0.86	D	0.543	neutral	None	None	None	None	N
S/E	0.9381	likely_pathogenic	0.9099	pathogenic	-1.757	Destabilizing	0.86	D	0.546	neutral	None	None	None	None	N
S/F	0.4277	ambiguous	0.3684	ambiguous	-0.684	Destabilizing	0.97	D	0.762	deleterious	N	0.506551607	None	None	N
S/G	0.216	likely_benign	0.148	benign	-0.712	Destabilizing	0.754	D	0.503	neutral	None	None	None	None	N
S/H	0.6931	likely_pathogenic	0.6204	pathogenic	-1.265	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
S/I	0.7134	likely_pathogenic	0.6239	pathogenic	0.166	Stabilizing	0.956	D	0.768	deleterious	None	None	None	None	N
S/K	0.9793	likely_pathogenic	0.9662	pathogenic	-0.706	Destabilizing	0.86	D	0.553	neutral	None	None	None	None	N
S/L	0.3609	ambiguous	0.2952	benign	0.166	Stabilizing	0.754	D	0.675	neutral	None	None	None	None	N
S/M	0.4445	ambiguous	0.3874	ambiguous	0.356	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
S/N	0.5363	ambiguous	0.4499	ambiguous	-1.171	Destabilizing	0.978	D	0.567	neutral	None	None	None	None	N
S/P	0.9957	likely_pathogenic	0.9945	pathogenic	-0.004	Destabilizing	0.014	N	0.386	neutral	D	0.54522888	None	None	N
S/Q	0.877	likely_pathogenic	0.8213	pathogenic	-1.297	Destabilizing	0.978	D	0.621	neutral	None	None	None	None	N
S/R	0.9581	likely_pathogenic	0.9288	pathogenic	-0.638	Destabilizing	0.978	D	0.749	deleterious	None	None	None	None	N
S/T	0.1685	likely_benign	0.1512	benign	-0.859	Destabilizing	0.822	D	0.512	neutral	D	0.528221367	None	None	N
S/V	0.6305	likely_pathogenic	0.5519	ambiguous	-0.004	Destabilizing	0.754	D	0.695	prob.neutral	None	None	None	None	N
S/W	0.7277	likely_pathogenic	0.6749	pathogenic	-0.877	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	N
S/Y	0.456	ambiguous	0.3955	ambiguous	-0.458	Destabilizing	0.99	D	0.759	deleterious	N	0.505537649	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.