TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7155	21688;21689;21690	chr2:178723637;178723636;178723635	chr2:179588364;179588363;179588362
N2AB	6838	20737;20738;20739	chr2:178723637;178723636;178723635	chr2:179588364;179588363;179588362
N2A	5911	17956;17957;17958	chr2:178723637;178723636;178723635	chr2:179588364;179588363;179588362
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-56
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4491
• 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
T/A	None	None	0.139	N	0.391	0.202	0.104622674875	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
T/A	0.1137	likely_benign	0.1076	benign	-0.731	Destabilizing	0.139	N	0.391	neutral	N	0.485156356	None	None	N
T/C	0.5382	ambiguous	0.5256	ambiguous	-0.564	Destabilizing	0.995	D	0.495	neutral	None	None	None	None	N
T/D	0.6135	likely_pathogenic	0.5996	pathogenic	0.061	Stabilizing	0.704	D	0.495	neutral	None	None	None	None	N
T/E	0.5143	ambiguous	0.4893	ambiguous	0.106	Stabilizing	0.329	N	0.472	neutral	None	None	None	None	N
T/F	0.3213	likely_benign	0.3164	benign	-0.774	Destabilizing	0.944	D	0.524	neutral	None	None	None	None	N
T/G	0.4265	ambiguous	0.4135	ambiguous	-1.016	Destabilizing	0.329	N	0.488	neutral	None	None	None	None	N
T/H	0.3295	likely_benign	0.312	benign	-1.167	Destabilizing	0.017	N	0.462	neutral	None	None	None	None	N
T/I	0.1672	likely_benign	0.1753	benign	-0.057	Destabilizing	0.927	D	0.566	neutral	N	0.462163802	None	None	N
T/K	0.2525	likely_benign	0.2353	benign	-0.527	Destabilizing	0.329	N	0.469	neutral	None	None	None	None	N
T/L	0.133	likely_benign	0.136	benign	-0.057	Destabilizing	0.704	D	0.501	neutral	None	None	None	None	N
T/M	0.1119	likely_benign	0.1115	benign	-0.065	Destabilizing	0.981	D	0.514	neutral	None	None	None	None	N
T/N	0.2087	likely_benign	0.2027	benign	-0.638	Destabilizing	0.642	D	0.464	neutral	N	0.459974983	None	None	N
T/P	0.4043	ambiguous	0.3993	ambiguous	-0.248	Destabilizing	0.006	N	0.352	neutral	N	0.520403814	None	None	N
T/Q	0.3222	likely_benign	0.3025	benign	-0.649	Destabilizing	0.085	N	0.395	neutral	None	None	None	None	N
T/R	0.183	likely_benign	0.1683	benign	-0.408	Destabilizing	0.003	N	0.319	neutral	None	None	None	None	N
T/S	0.162	likely_benign	0.158	benign	-0.949	Destabilizing	0.01	N	0.329	neutral	N	0.490785194	None	None	N
T/V	0.16	likely_benign	0.1622	benign	-0.248	Destabilizing	0.704	D	0.461	neutral	None	None	None	None	N
T/W	0.7025	likely_pathogenic	0.6923	pathogenic	-0.765	Destabilizing	0.995	D	0.546	neutral	None	None	None	None	N
T/Y	0.3765	ambiguous	0.3629	ambiguous	-0.482	Destabilizing	0.893	D	0.539	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.