TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7394	22405;22406;22407	chr2:178722719;178722718;178722717	chr2:179587446;179587445;179587444
N2AB	7077	21454;21455;21456	chr2:178722719;178722718;178722717	chr2:179587446;179587445;179587444
N2A	6150	18673;18674;18675	chr2:178722719;178722718;178722717	chr2:179587446;179587445;179587444
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: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-58
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1593
• 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/K	None	None	0.45	N	0.585	0.231	0.352262096564	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.0775	likely_benign	0.0876	benign	-1.74	Destabilizing	None	N	0.291	neutral	N	0.464774376	None	None	N
T/C	0.2997	likely_benign	0.3568	ambiguous	-1.04	Destabilizing	0.92	D	0.617	neutral	None	None	None	None	N
T/D	0.3504	ambiguous	0.4708	ambiguous	-1.692	Destabilizing	0.189	N	0.574	neutral	None	None	None	None	N
T/E	0.2492	likely_benign	0.3377	benign	-1.441	Destabilizing	0.02	N	0.425	neutral	None	None	None	None	N
T/F	0.1386	likely_benign	0.169	benign	-1.357	Destabilizing	0.953	D	0.623	neutral	None	None	None	None	N
T/G	0.2304	likely_benign	0.2948	benign	-2.131	Highly Destabilizing	0.005	N	0.461	neutral	None	None	None	None	N
T/H	0.1905	likely_benign	0.2323	benign	-1.855	Destabilizing	0.939	D	0.621	neutral	None	None	None	None	N
T/I	0.0736	likely_benign	0.0911	benign	-0.676	Destabilizing	0.002	N	0.385	neutral	N	0.487880962	None	None	N
T/K	0.2114	likely_benign	0.2842	benign	-0.283	Destabilizing	0.45	N	0.585	neutral	N	0.503330417	None	None	N
T/L	0.0719	likely_benign	0.0867	benign	-0.676	Destabilizing	0.309	N	0.515	neutral	None	None	None	None	N
T/M	0.0787	likely_benign	0.0867	benign	-0.825	Destabilizing	0.884	D	0.622	neutral	None	None	None	None	N
T/N	0.1196	likely_benign	0.1473	benign	-1.018	Destabilizing	0.189	N	0.549	neutral	None	None	None	None	N
T/P	0.6104	likely_pathogenic	0.7672	pathogenic	-1.008	Destabilizing	0.416	N	0.635	neutral	N	0.506858689	None	None	N
T/Q	0.2032	likely_benign	0.2609	benign	-0.769	Destabilizing	0.78	D	0.631	neutral	None	None	None	None	N
T/R	0.1409	likely_benign	0.1921	benign	-0.538	Destabilizing	0.939	D	0.631	neutral	N	0.492574706	None	None	N
T/S	0.0932	likely_benign	0.1026	benign	-1.338	Destabilizing	0.002	N	0.295	neutral	N	0.442743318	None	None	N
T/V	0.0852	likely_benign	0.0972	benign	-1.008	Destabilizing	0.02	N	0.292	neutral	None	None	None	None	N
T/W	0.4155	ambiguous	0.5117	ambiguous	-1.391	Destabilizing	0.998	D	0.658	neutral	None	None	None	None	N
T/Y	0.179	likely_benign	0.2206	benign	-1.069	Destabilizing	0.992	D	0.614	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.