TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26104	78535;78536;78537	chr2:178567822;178567821;178567820	chr2:179432549;179432548;179432547
N2AB	24463	73612;73613;73614	chr2:178567822;178567821;178567820	chr2:179432549;179432548;179432547
N2A	23536	70831;70832;70833	chr2:178567822;178567821;178567820	chr2:179432549;179432548;179432547
N2B	17039	51340;51341;51342	chr2:178567822;178567821;178567820	chr2:179432549;179432548;179432547
Novex-1	17164	51715;51716;51717	chr2:178567822;178567821;178567820	chr2:179432549;179432548;179432547
Novex-2	17231	51916;51917;51918	chr2:178567822;178567821;178567820	chr2:179432549;179432548;179432547
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-78
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.2427
• 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
E/G	None	None	0.27	N	0.357	0.197	0.287603790349	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
E/A	0.1028	likely_benign	0.1239	benign	-0.808	Destabilizing	0.002	N	0.202	neutral	N	0.382492654	None	None	N
E/C	0.5919	likely_pathogenic	0.6566	pathogenic	-0.599	Destabilizing	0.995	D	0.624	neutral	None	None	None	None	N
E/D	0.1489	likely_benign	0.1853	benign	-1.468	Destabilizing	0.425	N	0.41	neutral	N	0.46247359	None	None	N
E/F	0.6145	likely_pathogenic	0.6651	pathogenic	-0.868	Destabilizing	0.981	D	0.643	neutral	None	None	None	None	N
E/G	0.1746	likely_benign	0.2211	benign	-1.159	Destabilizing	0.27	N	0.357	neutral	N	0.423955275	None	None	N
E/H	0.3309	likely_benign	0.3984	ambiguous	-1.197	Destabilizing	0.981	D	0.543	neutral	None	None	None	None	N
E/I	0.3253	likely_benign	0.3902	ambiguous	0.143	Stabilizing	0.893	D	0.668	neutral	None	None	None	None	N
E/K	0.2267	likely_benign	0.293	benign	-0.91	Destabilizing	0.425	N	0.457	neutral	N	0.447600138	None	None	N
E/L	0.369	ambiguous	0.446	ambiguous	0.143	Stabilizing	0.704	D	0.559	neutral	None	None	None	None	N
E/M	0.3309	likely_benign	0.3787	ambiguous	0.646	Stabilizing	0.981	D	0.619	neutral	None	None	None	None	N
E/N	0.196	likely_benign	0.2496	benign	-1.162	Destabilizing	0.704	D	0.479	neutral	None	None	None	None	N
E/P	0.9815	likely_pathogenic	0.9879	pathogenic	-0.153	Destabilizing	0.828	D	0.591	neutral	None	None	None	None	N
E/Q	0.123	likely_benign	0.1451	benign	-1.017	Destabilizing	0.784	D	0.475	neutral	N	0.432150683	None	None	N
E/R	0.3467	ambiguous	0.4253	ambiguous	-0.859	Destabilizing	0.704	D	0.532	neutral	None	None	None	None	N
E/S	0.1019	likely_benign	0.1254	benign	-1.599	Destabilizing	0.004	N	0.119	neutral	None	None	None	None	N
E/T	0.1258	likely_benign	0.1586	benign	-1.297	Destabilizing	0.329	N	0.414	neutral	None	None	None	None	N
E/V	0.2071	likely_benign	0.2413	benign	-0.153	Destabilizing	0.473	N	0.527	neutral	N	0.443965187	None	None	N
E/W	0.855	likely_pathogenic	0.8878	pathogenic	-0.937	Destabilizing	0.995	D	0.661	neutral	None	None	None	None	N
E/Y	0.471	ambiguous	0.522	ambiguous	-0.677	Destabilizing	0.981	D	0.637	neutral	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.