TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25741	77446;77447;77448	chr2:178568911;178568910;178568909	chr2:179433638;179433637;179433636
N2AB	24100	72523;72524;72525	chr2:178568911;178568910;178568909	chr2:179433638;179433637;179433636
N2A	23173	69742;69743;69744	chr2:178568911;178568910;178568909	chr2:179433638;179433637;179433636
N2B	16676	50251;50252;50253	chr2:178568911;178568910;178568909	chr2:179433638;179433637;179433636
Novex-1	16801	50626;50627;50628	chr2:178568911;178568910;178568909	chr2:179433638;179433637;179433636
Novex-2	16868	50827;50828;50829	chr2:178568911;178568910;178568909	chr2:179433638;179433637;179433636
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-75
• Domain position: 44
• Structural Position: 51
• Q(SASA): 0.792
• 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/Y	rs756616171	0.781	0.065	N	0.309	0.127	0.214338557667	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/Y	rs756616171	0.781	0.065	N	0.309	0.127	0.214338557667	gnomAD-4.0.0	2.73763E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63865E-05	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
H/A	0.1195	likely_benign	0.1	benign	0.304	Stabilizing	0.004	N	0.31	neutral	None	None	None	None	N
H/C	0.1552	likely_benign	0.1473	benign	0.356	Stabilizing	0.497	N	0.236	neutral	None	None	None	None	N
H/D	0.0748	likely_benign	0.0643	benign	-0.221	Destabilizing	None	N	0.155	neutral	N	0.313840645	None	None	N
H/E	0.1571	likely_benign	0.1313	benign	-0.233	Destabilizing	0.002	N	0.236	neutral	None	None	None	None	N
H/F	0.2393	likely_benign	0.2247	benign	0.635	Stabilizing	0.22	N	0.288	neutral	None	None	None	None	N
H/G	0.0737	likely_benign	0.0679	benign	0.135	Stabilizing	None	N	0.174	neutral	None	None	None	None	N
H/I	0.2277	likely_benign	0.197	benign	0.703	Stabilizing	0.085	N	0.341	neutral	None	None	None	None	N
H/K	0.1471	likely_benign	0.128	benign	0.246	Stabilizing	0.004	N	0.362	neutral	None	None	None	None	N
H/L	0.0947	likely_benign	0.0898	benign	0.703	Stabilizing	0.014	N	0.286	neutral	N	0.390514705	None	None	N
H/M	0.3157	likely_benign	0.2857	benign	0.428	Stabilizing	0.245	N	0.256	neutral	None	None	None	None	N
H/N	0.0391	likely_benign	0.0347	benign	0.14	Stabilizing	None	N	0.128	neutral	N	0.348433222	None	None	N
H/P	0.1528	likely_benign	0.1568	benign	0.59	Stabilizing	0.065	N	0.324	neutral	N	0.380529784	None	None	N
H/Q	0.1049	likely_benign	0.0897	benign	0.162	Stabilizing	None	N	0.149	neutral	N	0.386684966	None	None	N
H/R	0.0977	likely_benign	0.0891	benign	-0.086	Destabilizing	None	N	0.137	neutral	N	0.378065482	None	None	N
H/S	0.0909	likely_benign	0.0778	benign	0.203	Stabilizing	0.004	N	0.317	neutral	None	None	None	None	N
H/T	0.1136	likely_benign	0.094	benign	0.273	Stabilizing	0.009	N	0.308	neutral	None	None	None	None	N
H/V	0.1697	likely_benign	0.1477	benign	0.59	Stabilizing	0.018	N	0.275	neutral	None	None	None	None	N
H/W	0.4039	ambiguous	0.3982	ambiguous	0.481	Stabilizing	0.788	D	0.255	neutral	None	None	None	None	N
H/Y	0.0816	likely_benign	0.0766	benign	0.757	Stabilizing	0.065	N	0.309	neutral	N	0.423896559	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.