TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25810	77653;77654;77655	chr2:178568704;178568703;178568702	chr2:179433431;179433430;179433429
N2AB	24169	72730;72731;72732	chr2:178568704;178568703;178568702	chr2:179433431;179433430;179433429
N2A	23242	69949;69950;69951	chr2:178568704;178568703;178568702	chr2:179433431;179433430;179433429
N2B	16745	50458;50459;50460	chr2:178568704;178568703;178568702	chr2:179433431;179433430;179433429
Novex-1	16870	50833;50834;50835	chr2:178568704;178568703;178568702	chr2:179433431;179433430;179433429
Novex-2	16937	51034;51035;51036	chr2:178568704;178568703;178568702	chr2:179433431;179433430;179433429
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-136
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.57
• 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/H	None	None	0.939	N	0.372	0.358	0.352910780287	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
Q/P	None	None	0.979	N	0.425	0.481	0.397391247328	gnomAD-4.0.0	1.59226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85971E-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
Q/A	0.2041	likely_benign	0.1859	benign	-0.098	Destabilizing	0.543	D	0.425	neutral	None	None	None	None	N
Q/C	0.6904	likely_pathogenic	0.6511	pathogenic	0.006	Stabilizing	0.996	D	0.495	neutral	None	None	None	None	N
Q/D	0.657	likely_pathogenic	0.6491	pathogenic	0.007	Stabilizing	0.854	D	0.399	neutral	None	None	None	None	N
Q/E	0.1265	likely_benign	0.132	benign	-0.04	Destabilizing	0.472	N	0.411	neutral	N	0.482918725	None	None	N
Q/F	0.7304	likely_pathogenic	0.7058	pathogenic	-0.436	Destabilizing	0.953	D	0.477	neutral	None	None	None	None	N
Q/G	0.4194	ambiguous	0.403	ambiguous	-0.229	Destabilizing	0.742	D	0.492	neutral	None	None	None	None	N
Q/H	0.2901	likely_benign	0.2628	benign	-0.069	Destabilizing	0.939	D	0.372	neutral	N	0.517071371	None	None	N
Q/I	0.3538	ambiguous	0.3392	benign	0.149	Stabilizing	0.082	N	0.44	neutral	None	None	None	None	N
Q/K	0.1099	likely_benign	0.106	benign	0.089	Stabilizing	0.309	N	0.423	neutral	N	0.406708813	None	None	N
Q/L	0.1107	likely_benign	0.1033	benign	0.149	Stabilizing	0.309	N	0.47	neutral	N	0.444093765	None	None	N
Q/M	0.2954	likely_benign	0.2868	benign	0.228	Stabilizing	0.953	D	0.374	neutral	None	None	None	None	N
Q/N	0.41	ambiguous	0.3835	ambiguous	-0.258	Destabilizing	0.742	D	0.375	neutral	None	None	None	None	N
Q/P	0.1233	likely_benign	0.113	benign	0.093	Stabilizing	0.979	D	0.425	neutral	N	0.49390651	None	None	N
Q/R	0.1289	likely_benign	0.1227	benign	0.253	Stabilizing	0.007	N	0.291	neutral	N	0.44645928	None	None	N
Q/S	0.3196	likely_benign	0.3013	benign	-0.225	Destabilizing	0.742	D	0.394	neutral	None	None	None	None	N
Q/T	0.2395	likely_benign	0.2277	benign	-0.135	Destabilizing	0.742	D	0.457	neutral	None	None	None	None	N
Q/V	0.215	likely_benign	0.2079	benign	0.093	Stabilizing	0.59	D	0.471	neutral	None	None	None	None	N
Q/W	0.6985	likely_pathogenic	0.6813	pathogenic	-0.475	Destabilizing	0.996	D	0.542	neutral	None	None	None	None	N
Q/Y	0.5583	ambiguous	0.5338	ambiguous	-0.191	Destabilizing	0.984	D	0.41	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.