TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7539	22840;22841;22842	chr2:178722048;178722047;178722046	chr2:179586775;179586774;179586773
N2AB	7222	21889;21890;21891	chr2:178722048;178722047;178722046	chr2:179586775;179586774;179586773
N2A	6295	19108;19109;19110	chr2:178722048;178722047;178722046	chr2:179586775;179586774;179586773
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: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-60
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3148
• 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/N	rs879209114	None	0.826	N	0.496	0.261	0.506613155829	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	None	0	0	0	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	0.1044	likely_benign	0.1344	benign	-0.937	Destabilizing	0.083	N	0.443	neutral	N	0.486132389	None	None	I
T/C	0.6429	likely_pathogenic	0.7563	pathogenic	-0.355	Destabilizing	0.998	D	0.562	neutral	None	None	None	None	I
T/D	0.4876	ambiguous	0.6087	pathogenic	-0.584	Destabilizing	0.862	D	0.501	neutral	None	None	None	None	I
T/E	0.3495	ambiguous	0.4341	ambiguous	-0.523	Destabilizing	0.954	D	0.515	neutral	None	None	None	None	I
T/F	0.2612	likely_benign	0.3942	ambiguous	-0.726	Destabilizing	0.987	D	0.609	neutral	None	None	None	None	I
T/G	0.3716	ambiguous	0.4433	ambiguous	-1.269	Destabilizing	0.882	D	0.527	neutral	None	None	None	None	I
T/H	0.3177	likely_benign	0.4382	ambiguous	-1.479	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	I
T/I	0.1725	likely_benign	0.3299	benign	-0.114	Destabilizing	0.044	N	0.241	neutral	N	0.480726569	None	None	I
T/K	0.2483	likely_benign	0.3146	benign	-0.871	Destabilizing	0.967	D	0.503	neutral	None	None	None	None	I
T/L	0.1194	likely_benign	0.1928	benign	-0.114	Destabilizing	0.589	D	0.477	neutral	None	None	None	None	I
T/M	0.0936	likely_benign	0.1175	benign	0.199	Stabilizing	0.991	D	0.573	neutral	None	None	None	None	I
T/N	0.1705	likely_benign	0.2392	benign	-0.947	Destabilizing	0.826	D	0.496	neutral	N	0.503699429	None	None	I
T/P	0.5802	likely_pathogenic	0.6755	pathogenic	-0.356	Destabilizing	0.906	D	0.569	neutral	N	0.5111181	None	None	I
T/Q	0.2541	likely_benign	0.3215	benign	-0.956	Destabilizing	0.965	D	0.57	neutral	None	None	None	None	I
T/R	0.1724	likely_benign	0.2308	benign	-0.741	Destabilizing	0.987	D	0.573	neutral	None	None	None	None	I
T/S	0.1171	likely_benign	0.14	benign	-1.19	Destabilizing	0.006	N	0.151	neutral	N	0.463370172	None	None	I
T/V	0.1586	likely_benign	0.2635	benign	-0.356	Destabilizing	0.506	D	0.451	neutral	None	None	None	None	I
T/W	0.6128	likely_pathogenic	0.7307	pathogenic	-0.758	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
T/Y	0.3718	ambiguous	0.5022	ambiguous	-0.53	Destabilizing	0.994	D	0.619	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.