TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27095	81508;81509;81510	chr2:178564849;178564848;178564847	chr2:179429576;179429575;179429574
N2AB	25454	76585;76586;76587	chr2:178564849;178564848;178564847	chr2:179429576;179429575;179429574
N2A	24527	73804;73805;73806	chr2:178564849;178564848;178564847	chr2:179429576;179429575;179429574
N2B	18030	54313;54314;54315	chr2:178564849;178564848;178564847	chr2:179429576;179429575;179429574
Novex-1	18155	54688;54689;54690	chr2:178564849;178564848;178564847	chr2:179429576;179429575;179429574
Novex-2	18222	54889;54890;54891	chr2:178564849;178564848;178564847	chr2:179429576;179429575;179429574
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: Fn3-85
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.567
• 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	rs1415718775	None	0.285	N	0.379	0.251	0.252681307341	gnomAD-4.0.0	1.36893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9959E-07	1.16044E-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
E/A	0.1543	likely_benign	0.137	benign	-0.164	Destabilizing	0.005	N	0.205	neutral	N	0.415794364	None	None	N
E/C	0.8115	likely_pathogenic	0.7935	pathogenic	-0.319	Destabilizing	0.991	D	0.462	neutral	None	None	None	None	N
E/D	0.3086	likely_benign	0.2766	benign	-1.016	Destabilizing	0.285	N	0.383	neutral	N	0.500261187	None	None	N
E/F	0.8262	likely_pathogenic	0.7957	pathogenic	0.564	Stabilizing	0.818	D	0.514	neutral	None	None	None	None	N
E/G	0.3207	likely_benign	0.2847	benign	-0.518	Destabilizing	0.001	N	0.301	neutral	N	0.491390988	None	None	N
E/H	0.5992	likely_pathogenic	0.5737	pathogenic	0.618	Stabilizing	0.965	D	0.513	neutral	None	None	None	None	N
E/I	0.2781	likely_benign	0.2495	benign	0.791	Stabilizing	0.39	N	0.507	neutral	None	None	None	None	N
E/K	0.12	likely_benign	0.117	benign	-0.061	Destabilizing	0.285	N	0.379	neutral	N	0.427667583	None	None	N
E/L	0.3666	ambiguous	0.3304	benign	0.791	Stabilizing	0.209	N	0.353	neutral	None	None	None	None	N
E/M	0.4152	ambiguous	0.3752	ambiguous	0.781	Stabilizing	0.103	N	0.323	neutral	None	None	None	None	N
E/N	0.4726	ambiguous	0.439	ambiguous	-0.75	Destabilizing	0.561	D	0.457	neutral	None	None	None	None	N
E/P	0.3485	ambiguous	0.3293	benign	0.495	Stabilizing	0.002	N	0.191	neutral	None	None	None	None	N
E/Q	0.1372	likely_benign	0.1313	benign	-0.557	Destabilizing	0.662	D	0.457	neutral	N	0.482502146	None	None	N
E/R	0.2385	likely_benign	0.2331	benign	0.311	Stabilizing	0.722	D	0.462	neutral	None	None	None	None	N
E/S	0.298	likely_benign	0.2694	benign	-0.954	Destabilizing	0.209	N	0.376	neutral	None	None	None	None	N
E/T	0.2668	likely_benign	0.2427	benign	-0.636	Destabilizing	0.345	N	0.415	neutral	None	None	None	None	N
E/V	0.1634	likely_benign	0.1542	benign	0.495	Stabilizing	0.003	N	0.329	neutral	N	0.478827122	None	None	N
E/W	0.9552	likely_pathogenic	0.9478	pathogenic	0.775	Stabilizing	0.991	D	0.501	neutral	None	None	None	None	N
E/Y	0.7207	likely_pathogenic	0.7006	pathogenic	0.836	Stabilizing	0.965	D	0.52	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.