TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6890	20893;20894;20895	chr2:178725536;178725535;178725534	chr2:179590263;179590262;179590261
N2AB	6573	19942;19943;19944	chr2:178725536;178725535;178725534	chr2:179590263;179590262;179590261
N2A	5646	17161;17162;17163	chr2:178725536;178725535;178725534	chr2:179590263;179590262;179590261
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-53
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.5575
• 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/K	None	None	0.324	N	0.445	0.235	0.231231049324	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	0.2162	likely_benign	0.2558	benign	-0.63	Destabilizing	0.324	N	0.416	neutral	N	0.507464013	None	None	N
E/C	0.8775	likely_pathogenic	0.8816	pathogenic	-0.311	Destabilizing	0.981	D	0.535	neutral	None	None	None	None	N
E/D	0.0661	likely_benign	0.0652	benign	-0.69	Destabilizing	None	N	0.163	neutral	N	0.311922556	None	None	N
E/F	0.7958	likely_pathogenic	0.83	pathogenic	-0.242	Destabilizing	0.932	D	0.498	neutral	None	None	None	None	N
E/G	0.0829	likely_benign	0.1022	benign	-0.928	Destabilizing	0.324	N	0.453	neutral	N	0.449010356	None	None	N
E/H	0.6203	likely_pathogenic	0.6649	pathogenic	-0.356	Destabilizing	0.932	D	0.369	neutral	None	None	None	None	N
E/I	0.6363	likely_pathogenic	0.6618	pathogenic	0.155	Stabilizing	0.818	D	0.505	neutral	None	None	None	None	N
E/K	0.3251	likely_benign	0.3835	ambiguous	-0.286	Destabilizing	0.324	N	0.445	neutral	N	0.488531536	None	None	N
E/L	0.5514	ambiguous	0.5935	pathogenic	0.155	Stabilizing	0.818	D	0.454	neutral	None	None	None	None	N
E/M	0.6466	likely_pathogenic	0.6776	pathogenic	0.395	Stabilizing	0.981	D	0.49	neutral	None	None	None	None	N
E/N	0.162	likely_benign	0.1837	benign	-0.648	Destabilizing	0.241	N	0.404	neutral	None	None	None	None	N
E/P	0.7918	likely_pathogenic	0.8304	pathogenic	-0.085	Destabilizing	0.818	D	0.405	neutral	None	None	None	None	N
E/Q	0.2405	likely_benign	0.2715	benign	-0.555	Destabilizing	0.324	N	0.431	neutral	N	0.478277257	None	None	N
E/R	0.4262	ambiguous	0.5039	ambiguous	-0.014	Destabilizing	0.69	D	0.359	neutral	None	None	None	None	N
E/S	0.2249	likely_benign	0.2441	benign	-0.89	Destabilizing	0.116	N	0.401	neutral	None	None	None	None	N
E/T	0.3912	ambiguous	0.42	ambiguous	-0.653	Destabilizing	0.388	N	0.43	neutral	None	None	None	None	N
E/V	0.3985	ambiguous	0.4374	ambiguous	-0.085	Destabilizing	0.773	D	0.448	neutral	N	0.465060031	None	None	N
E/W	0.8885	likely_pathogenic	0.9174	pathogenic	-0.034	Destabilizing	0.981	D	0.59	neutral	None	None	None	None	N
E/Y	0.6053	likely_pathogenic	0.6621	pathogenic	-0.009	Destabilizing	0.932	D	0.485	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.