TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18753	56482;56483;56484	chr2:178599644;178599643;178599642	chr2:179464371;179464370;179464369
N2AB	17112	51559;51560;51561	chr2:178599644;178599643;178599642	chr2:179464371;179464370;179464369
N2A	16185	48778;48779;48780	chr2:178599644;178599643;178599642	chr2:179464371;179464370;179464369
N2B	9688	29287;29288;29289	chr2:178599644;178599643;178599642	chr2:179464371;179464370;179464369
Novex-1	9813	29662;29663;29664	chr2:178599644;178599643;178599642	chr2:179464371;179464370;179464369
Novex-2	9880	29863;29864;29865	chr2:178599644;178599643;178599642	chr2:179464371;179464370;179464369
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-116
• Domain position: 66
• Structural Position: 143
• Q(SASA): 0.7504
• 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
Q/E	None	None	0.4	N	0.199	0.158	0.119812018005	gnomAD-4.0.0	1.59342E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43592E-05	0
Q/R	None	None	0.98	N	0.491	0.27	0.154104182512	gnomAD-4.0.0	1.59343E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43625E-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
Q/A	0.2018	likely_benign	0.1954	benign	-0.272	Destabilizing	0.985	D	0.481	neutral	None	None	None	None	N
Q/C	0.6397	likely_pathogenic	0.6212	pathogenic	0.392	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
Q/D	0.2251	likely_benign	0.2242	benign	-0.611	Destabilizing	0.971	D	0.471	neutral	None	None	None	None	N
Q/E	0.0722	likely_benign	0.0738	benign	-0.601	Destabilizing	0.4	N	0.199	neutral	N	0.44989579	None	None	N
Q/F	0.6515	likely_pathogenic	0.6285	pathogenic	-0.395	Destabilizing	0.998	D	0.543	neutral	None	None	None	None	N
Q/G	0.2131	likely_benign	0.2073	benign	-0.536	Destabilizing	0.993	D	0.487	neutral	None	None	None	None	N
Q/H	0.2173	likely_benign	0.2071	benign	-0.703	Destabilizing	0.265	N	0.299	neutral	N	0.480104054	None	None	N
Q/I	0.4785	ambiguous	0.4676	ambiguous	0.355	Stabilizing	0.999	D	0.537	neutral	None	None	None	None	N
Q/K	0.0978	likely_benign	0.095	benign	-0.095	Destabilizing	0.98	D	0.509	neutral	N	0.432502108	None	None	N
Q/L	0.1654	likely_benign	0.1635	benign	0.355	Stabilizing	0.99	D	0.451	neutral	N	0.470731723	None	None	N
Q/M	0.371	ambiguous	0.3785	ambiguous	0.963	Stabilizing	0.999	D	0.435	neutral	None	None	None	None	N
Q/N	0.1855	likely_benign	0.1848	benign	-0.463	Destabilizing	0.985	D	0.461	neutral	None	None	None	None	N
Q/P	0.3646	ambiguous	0.337	benign	0.177	Stabilizing	0.999	D	0.427	neutral	N	0.480834773	None	None	N
Q/R	0.1114	likely_benign	0.1061	benign	0.023	Stabilizing	0.98	D	0.491	neutral	N	0.460555501	None	None	N
Q/S	0.2029	likely_benign	0.1934	benign	-0.431	Destabilizing	0.985	D	0.473	neutral	None	None	None	None	N
Q/T	0.2173	likely_benign	0.2072	benign	-0.258	Destabilizing	0.993	D	0.445	neutral	None	None	None	None	N
Q/V	0.3095	likely_benign	0.296	benign	0.177	Stabilizing	0.998	D	0.428	neutral	None	None	None	None	N
Q/W	0.6039	likely_pathogenic	0.5965	pathogenic	-0.387	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	N
Q/Y	0.4163	ambiguous	0.3913	ambiguous	-0.115	Destabilizing	0.996	D	0.45	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.