TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27502	82729;82730;82731	chr2:178563628;178563627;178563626	chr2:179428355;179428354;179428353
N2AB	25861	77806;77807;77808	chr2:178563628;178563627;178563626	chr2:179428355;179428354;179428353
N2A	24934	75025;75026;75027	chr2:178563628;178563627;178563626	chr2:179428355;179428354;179428353
N2B	18437	55534;55535;55536	chr2:178563628;178563627;178563626	chr2:179428355;179428354;179428353
Novex-1	18562	55909;55910;55911	chr2:178563628;178563627;178563626	chr2:179428355;179428354;179428353
Novex-2	18629	56110;56111;56112	chr2:178563628;178563627;178563626	chr2:179428355;179428354;179428353
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-88
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.6848
• Predicted PPI site: I

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
E/A	None	None	0.805	N	0.581	0.355	0.304760801415	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
E/A	0.1066	likely_benign	0.1071	benign	-0.457	Destabilizing	0.805	D	0.581	neutral	N	0.478480406	None	None	I
E/C	0.588	likely_pathogenic	0.6034	pathogenic	-0.043	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	I
E/D	0.1378	likely_benign	0.1379	benign	-0.503	Destabilizing	0.025	N	0.216	neutral	N	0.416237081	None	None	I
E/F	0.5651	likely_pathogenic	0.5902	pathogenic	-0.366	Destabilizing	0.987	D	0.749	deleterious	None	None	None	None	I
E/G	0.1346	likely_benign	0.1322	benign	-0.686	Destabilizing	0.892	D	0.577	neutral	N	0.47628825	None	None	I
E/H	0.2669	likely_benign	0.2979	benign	-0.343	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	I
E/I	0.2046	likely_benign	0.2005	benign	0.119	Stabilizing	0.975	D	0.748	deleterious	None	None	None	None	I
E/K	0.0893	likely_benign	0.0975	benign	0.095	Stabilizing	0.892	D	0.575	neutral	N	0.443559756	None	None	I
E/L	0.2078	likely_benign	0.2198	benign	0.119	Stabilizing	0.95	D	0.637	neutral	None	None	None	None	I
E/M	0.2846	likely_benign	0.2991	benign	0.335	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
E/N	0.175	likely_benign	0.187	benign	-0.138	Destabilizing	0.975	D	0.591	neutral	None	None	None	None	I
E/P	0.6995	likely_pathogenic	0.6999	pathogenic	-0.052	Destabilizing	0.987	D	0.673	neutral	None	None	None	None	I
E/Q	0.0987	likely_benign	0.1071	benign	-0.113	Destabilizing	0.983	D	0.596	neutral	N	0.397942109	None	None	I
E/R	0.1387	likely_benign	0.1566	benign	0.28	Stabilizing	0.975	D	0.61	neutral	None	None	None	None	I
E/S	0.1218	likely_benign	0.1317	benign	-0.346	Destabilizing	0.845	D	0.548	neutral	None	None	None	None	I
E/T	0.1081	likely_benign	0.1169	benign	-0.169	Destabilizing	0.073	N	0.315	neutral	None	None	None	None	I
E/V	0.1333	likely_benign	0.1282	benign	-0.052	Destabilizing	0.935	D	0.574	neutral	N	0.453179316	None	None	I
E/W	0.7438	likely_pathogenic	0.7837	pathogenic	-0.229	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
E/Y	0.442	ambiguous	0.4616	ambiguous	-0.132	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	I

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.