TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3985	12178;12179;12180	chr2:178741280;178741279;178741278	chr2:179606007;179606006;179606005
N2AB	3668	11227;11228;11229	chr2:178741280;178741279;178741278	chr2:179606007;179606006;179606005
N2A	None	None	chr2:None	chr2:None
N2B	3622	11089;11090;11091	chr2:178741280;178741279;178741278	chr2:179606007;179606006;179606005
Novex-1	3747	11464;11465;11466	chr2:178741280;178741279;178741278	chr2:179606007;179606006;179606005
Novex-2	3814	11665;11666;11667	chr2:178741280;178741279;178741278	chr2:179606007;179606006;179606005
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-28
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3201
• 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
T/I	None	None	0.051	N	0.267	0.155	None	gnomAD-4.0.0	1.59118E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85786E-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
T/A	0.2383	likely_benign	0.2134	benign	-1.298	Destabilizing	0.454	N	0.285	neutral	N	0.507216827	None	None	I
T/C	0.7621	likely_pathogenic	0.7185	pathogenic	-0.949	Destabilizing	0.998	D	0.391	neutral	None	None	None	None	I
T/D	0.762	likely_pathogenic	0.7184	pathogenic	-0.658	Destabilizing	0.842	D	0.392	neutral	None	None	None	None	I
T/E	0.6659	likely_pathogenic	0.642	pathogenic	-0.553	Destabilizing	0.842	D	0.395	neutral	None	None	None	None	I
T/F	0.8036	likely_pathogenic	0.7669	pathogenic	-1.273	Destabilizing	0.016	N	0.332	neutral	None	None	None	None	I
T/G	0.6711	likely_pathogenic	0.6174	pathogenic	-1.613	Destabilizing	0.728	D	0.435	neutral	None	None	None	None	I
T/H	0.5219	ambiguous	0.5114	ambiguous	-1.755	Destabilizing	0.998	D	0.433	neutral	None	None	None	None	I
T/I	0.6483	likely_pathogenic	0.599	pathogenic	-0.509	Destabilizing	0.051	N	0.267	neutral	N	0.500052215	None	None	I
T/K	0.4844	ambiguous	0.492	ambiguous	-0.51	Destabilizing	0.842	D	0.394	neutral	None	None	None	None	I
T/L	0.4407	ambiguous	0.3968	ambiguous	-0.509	Destabilizing	0.525	D	0.383	neutral	None	None	None	None	I
T/M	0.2538	likely_benign	0.2355	benign	-0.349	Destabilizing	0.974	D	0.403	neutral	None	None	None	None	I
T/N	0.3391	likely_benign	0.317	benign	-0.788	Destabilizing	0.801	D	0.345	neutral	N	0.506043095	None	None	I
T/P	0.8511	likely_pathogenic	0.7665	pathogenic	-0.743	Destabilizing	0.966	D	0.411	neutral	D	0.566969828	None	None	I
T/Q	0.4726	ambiguous	0.4752	ambiguous	-0.839	Destabilizing	0.974	D	0.409	neutral	None	None	None	None	I
T/R	0.3661	ambiguous	0.3873	ambiguous	-0.495	Destabilizing	0.949	D	0.408	neutral	None	None	None	None	I
T/S	0.2436	likely_benign	0.2369	benign	-1.169	Destabilizing	0.022	N	0.107	neutral	N	0.475814559	None	None	I
T/V	0.4919	ambiguous	0.4461	ambiguous	-0.743	Destabilizing	0.067	N	0.099	neutral	None	None	None	None	I
T/W	0.9327	likely_pathogenic	0.9068	pathogenic	-1.189	Destabilizing	0.998	D	0.45	neutral	None	None	None	None	I
T/Y	0.74	likely_pathogenic	0.7031	pathogenic	-0.898	Destabilizing	0.904	D	0.447	neutral	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.