TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8426	25501;25502;25503	chr2:178717598;178717597;178717596	chr2:179582325;179582324;179582323
N2AB	8109	24550;24551;24552	chr2:178717598;178717597;178717596	chr2:179582325;179582324;179582323
N2A	7182	21769;21770;21771	chr2:178717598;178717597;178717596	chr2:179582325;179582324;179582323
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-69
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1811
• 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/Q	rs1409245989	-1.514	0.954	N	0.606	0.255	0.154104182512	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
H/Q	rs1409245989	-1.514	0.954	N	0.606	0.255	0.154104182512	gnomAD-4.0.0	1.59252E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43414E-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	0.7247	likely_pathogenic	0.615	pathogenic	-1.598	Destabilizing	0.931	D	0.643	neutral	None	None	None	None	N
H/C	0.5682	likely_pathogenic	0.4484	ambiguous	-0.869	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
H/D	0.3427	ambiguous	0.2397	benign	-1.202	Destabilizing	0.003	N	0.424	neutral	N	0.367029264	None	None	N
H/E	0.7421	likely_pathogenic	0.6318	pathogenic	-1.023	Destabilizing	0.737	D	0.492	neutral	None	None	None	None	N
H/F	0.617	likely_pathogenic	0.532	ambiguous	0.043	Stabilizing	0.901	D	0.699	prob.neutral	None	None	None	None	N
H/G	0.769	likely_pathogenic	0.6638	pathogenic	-2.035	Highly Destabilizing	0.931	D	0.642	neutral	None	None	None	None	N
H/I	0.7504	likely_pathogenic	0.6529	pathogenic	-0.328	Destabilizing	0.979	D	0.793	deleterious	None	None	None	None	N
H/K	0.7846	likely_pathogenic	0.7108	pathogenic	-1.014	Destabilizing	0.929	D	0.617	neutral	None	None	None	None	N
H/L	0.2923	likely_benign	0.2475	benign	-0.328	Destabilizing	0.831	D	0.719	prob.delet.	N	0.518031377	None	None	N
H/M	0.7572	likely_pathogenic	0.6868	pathogenic	-0.541	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
H/N	0.1781	likely_benign	0.1413	benign	-1.605	Destabilizing	0.04	N	0.317	neutral	N	0.50525408	None	None	N
H/P	0.7478	likely_pathogenic	0.6211	pathogenic	-0.738	Destabilizing	0.994	D	0.768	deleterious	N	0.500087282	None	None	N
H/Q	0.5085	ambiguous	0.4106	ambiguous	-1.246	Destabilizing	0.954	D	0.606	neutral	N	0.519588815	None	None	N
H/R	0.53	ambiguous	0.4428	ambiguous	-1.353	Destabilizing	0.952	D	0.589	neutral	N	0.511443587	None	None	N
H/S	0.5036	ambiguous	0.3991	ambiguous	-1.794	Destabilizing	0.931	D	0.593	neutral	None	None	None	None	N
H/T	0.7349	likely_pathogenic	0.6173	pathogenic	-1.476	Destabilizing	0.908	D	0.677	prob.neutral	None	None	None	None	N
H/V	0.6891	likely_pathogenic	0.5839	pathogenic	-0.738	Destabilizing	0.931	D	0.728	prob.delet.	None	None	None	None	N
H/W	0.7574	likely_pathogenic	0.6879	pathogenic	0.636	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
H/Y	0.225	likely_benign	0.182	benign	0.489	Stabilizing	0.041	N	0.297	neutral	N	0.511443587	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.