TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32068	96427;96428;96429	chr2:178543942;178543941;178543940	chr2:179408669;179408668;179408667
N2AB	30427	91504;91505;91506	chr2:178543942;178543941;178543940	chr2:179408669;179408668;179408667
N2A	29500	88723;88724;88725	chr2:178543942;178543941;178543940	chr2:179408669;179408668;179408667
N2B	23003	69232;69233;69234	chr2:178543942;178543941;178543940	chr2:179408669;179408668;179408667
Novex-1	23128	69607;69608;69609	chr2:178543942;178543941;178543940	chr2:179408669;179408668;179408667
Novex-2	23195	69808;69809;69810	chr2:178543942;178543941;178543940	chr2:179408669;179408668;179408667
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-153
• Domain position: 52
• Structural Position: 136
• Q(SASA): 0.1087
• 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/A	None	None	0.012	N	0.515	0.068	0.107399877778	gnomAD-4.0.0	3.18286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86549E-05	0
S/L	None	None	0.027	N	0.725	0.266	0.30212335484	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	5.65867E-05	0	None	0	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
S/A	0.2073	likely_benign	0.1997	benign	-0.894	Destabilizing	0.012	N	0.515	neutral	N	0.490513049	None	None	N
S/C	0.1631	likely_benign	0.1793	benign	-0.352	Destabilizing	0.824	D	0.73	prob.delet.	None	None	None	None	N
S/D	0.9744	likely_pathogenic	0.9743	pathogenic	-1.755	Destabilizing	0.149	N	0.701	prob.neutral	None	None	None	None	N
S/E	0.9902	likely_pathogenic	0.99	pathogenic	-1.442	Destabilizing	0.149	N	0.696	prob.neutral	None	None	None	None	N
S/F	0.937	likely_pathogenic	0.9366	pathogenic	-0.557	Destabilizing	0.555	D	0.79	deleterious	None	None	None	None	N
S/G	0.3524	ambiguous	0.3406	ambiguous	-1.344	Destabilizing	0.067	N	0.703	prob.neutral	None	None	None	None	N
S/H	0.9271	likely_pathogenic	0.9346	pathogenic	-1.434	Destabilizing	0.791	D	0.733	prob.delet.	None	None	None	None	N
S/I	0.8061	likely_pathogenic	0.8102	pathogenic	0.315	Stabilizing	0.081	N	0.768	deleterious	None	None	None	None	N
S/K	0.9969	likely_pathogenic	0.9971	pathogenic	0.376	Stabilizing	0.149	N	0.698	prob.neutral	None	None	None	None	N
S/L	0.6	likely_pathogenic	0.6023	pathogenic	0.315	Stabilizing	0.027	N	0.725	prob.delet.	N	0.463174079	None	None	N
S/M	0.6665	likely_pathogenic	0.6807	pathogenic	-0.095	Destabilizing	0.555	D	0.737	prob.delet.	None	None	None	None	N
S/N	0.7349	likely_pathogenic	0.7541	pathogenic	-0.696	Destabilizing	0.149	N	0.669	neutral	None	None	None	None	N
S/P	0.9818	likely_pathogenic	0.9766	pathogenic	-0.058	Destabilizing	0.211	N	0.752	deleterious	N	0.467101326	None	None	N
S/Q	0.9751	likely_pathogenic	0.976	pathogenic	-0.174	Destabilizing	0.555	D	0.753	deleterious	None	None	None	None	N
S/R	0.9939	likely_pathogenic	0.9943	pathogenic	-0.39	Destabilizing	0.149	N	0.761	deleterious	None	None	None	None	N
S/T	0.0864	likely_benign	0.1001	benign	-0.236	Destabilizing	None	N	0.331	neutral	N	0.390658272	None	None	N
S/V	0.6593	likely_pathogenic	0.6727	pathogenic	-0.058	Destabilizing	0.035	N	0.724	prob.delet.	None	None	None	None	N
S/W	0.969	likely_pathogenic	0.9695	pathogenic	-0.933	Destabilizing	0.935	D	0.76	deleterious	None	None	None	None	N
S/Y	0.9095	likely_pathogenic	0.9138	pathogenic	-0.44	Destabilizing	0.555	D	0.789	deleterious	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.