TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25981	78166;78167;78168	chr2:178568191;178568190;178568189	chr2:179432918;179432917;179432916
N2AB	24340	73243;73244;73245	chr2:178568191;178568190;178568189	chr2:179432918;179432917;179432916
N2A	23413	70462;70463;70464	chr2:178568191;178568190;178568189	chr2:179432918;179432917;179432916
N2B	16916	50971;50972;50973	chr2:178568191;178568190;178568189	chr2:179432918;179432917;179432916
Novex-1	17041	51346;51347;51348	chr2:178568191;178568190;178568189	chr2:179432918;179432917;179432916
Novex-2	17108	51547;51548;51549	chr2:178568191;178568190;178568189	chr2:179432918;179432917;179432916
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-76
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.4115
• 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
P/R	rs794729505	-0.133	0.314	N	0.711	0.367	0.360565625551	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
P/R	rs794729505	-0.133	0.314	N	0.711	0.367	0.360565625551	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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
P/A	0.0526	likely_benign	0.0486	benign	-0.933	Destabilizing	None	N	0.336	neutral	N	0.469204775	None	None	N
P/C	0.2405	likely_benign	0.2456	benign	-0.743	Destabilizing	0.823	D	0.773	deleterious	None	None	None	None	N
P/D	0.5207	ambiguous	0.5462	ambiguous	-0.669	Destabilizing	0.378	N	0.655	prob.neutral	None	None	None	None	N
P/E	0.3692	ambiguous	0.3789	ambiguous	-0.737	Destabilizing	0.147	N	0.619	neutral	None	None	None	None	N
P/F	0.4196	ambiguous	0.43	ambiguous	-0.86	Destabilizing	0.552	D	0.781	deleterious	None	None	None	None	N
P/G	0.2279	likely_benign	0.2363	benign	-1.155	Destabilizing	0.08	N	0.639	neutral	None	None	None	None	N
P/H	0.2069	likely_benign	0.2154	benign	-0.603	Destabilizing	0.934	D	0.711	prob.delet.	None	None	None	None	N
P/I	0.2423	likely_benign	0.2265	benign	-0.467	Destabilizing	0.378	N	0.761	deleterious	None	None	None	None	N
P/K	0.3316	likely_benign	0.3365	benign	-0.805	Destabilizing	0.147	N	0.623	neutral	None	None	None	None	N
P/L	0.1355	likely_benign	0.1369	benign	-0.467	Destabilizing	0.061	N	0.738	deleterious	N	0.490127695	None	None	N
P/M	0.2606	likely_benign	0.2524	benign	-0.421	Destabilizing	0.823	D	0.715	prob.delet.	None	None	None	None	N
P/N	0.2918	likely_benign	0.2792	benign	-0.558	Destabilizing	0.378	N	0.683	prob.neutral	None	None	None	None	N
P/Q	0.1938	likely_benign	0.1917	benign	-0.787	Destabilizing	0.314	N	0.665	prob.neutral	N	0.484811777	None	None	N
P/R	0.2329	likely_benign	0.2614	benign	-0.222	Destabilizing	0.314	N	0.711	prob.delet.	N	0.484811777	None	None	N
P/S	0.0989	likely_benign	0.0959	benign	-0.996	Destabilizing	0.002	N	0.377	neutral	N	0.470378211	None	None	N
P/T	0.0888	likely_benign	0.0826	benign	-0.957	Destabilizing	0.061	N	0.537	neutral	N	0.46617409	None	None	N
P/V	0.1565	likely_benign	0.144	benign	-0.586	Destabilizing	0.08	N	0.675	prob.neutral	None	None	None	None	N
P/W	0.6725	likely_pathogenic	0.7131	pathogenic	-0.96	Destabilizing	0.934	D	0.747	deleterious	None	None	None	None	N
P/Y	0.4216	ambiguous	0.4374	ambiguous	-0.677	Destabilizing	0.552	D	0.781	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.