TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27248	81967;81968;81969	chr2:178564390;178564389;178564388	chr2:179429117;179429116;179429115
N2AB	25607	77044;77045;77046	chr2:178564390;178564389;178564388	chr2:179429117;179429116;179429115
N2A	24680	74263;74264;74265	chr2:178564390;178564389;178564388	chr2:179429117;179429116;179429115
N2B	18183	54772;54773;54774	chr2:178564390;178564389;178564388	chr2:179429117;179429116;179429115
Novex-1	18308	55147;55148;55149	chr2:178564390;178564389;178564388	chr2:179429117;179429116;179429115
Novex-2	18375	55348;55349;55350	chr2:178564390;178564389;178564388	chr2:179429117;179429116;179429115
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-86
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2246
• 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
R/I	None	None	0.991	N	0.769	0.42	0.461323234107	gnomAD-4.0.0	7.95872E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.42921E-05	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
R/A	0.9182	likely_pathogenic	0.8847	pathogenic	-1.678	Destabilizing	0.953	D	0.571	neutral	None	None	None	None	N
R/C	0.436	ambiguous	0.3713	ambiguous	-1.793	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
R/D	0.9912	likely_pathogenic	0.9885	pathogenic	-0.796	Destabilizing	0.986	D	0.727	prob.delet.	None	None	None	None	N
R/E	0.8565	likely_pathogenic	0.8087	pathogenic	-0.676	Destabilizing	0.91	D	0.477	neutral	None	None	None	None	N
R/F	0.9069	likely_pathogenic	0.8729	pathogenic	-1.718	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
R/G	0.8926	likely_pathogenic	0.854	pathogenic	-1.954	Destabilizing	0.939	D	0.651	neutral	N	0.478334225	None	None	N
R/H	0.3286	likely_benign	0.2804	benign	-1.995	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
R/I	0.672	likely_pathogenic	0.5953	pathogenic	-0.921	Destabilizing	0.991	D	0.769	deleterious	N	0.464916463	None	None	N
R/K	0.1038	likely_benign	0.0932	benign	-1.611	Destabilizing	0.046	N	0.235	neutral	N	0.404908154	None	None	N
R/L	0.69	likely_pathogenic	0.6258	pathogenic	-0.921	Destabilizing	0.953	D	0.651	neutral	None	None	None	None	N
R/M	0.7113	likely_pathogenic	0.6312	pathogenic	-1.024	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
R/N	0.9683	likely_pathogenic	0.9574	pathogenic	-1.109	Destabilizing	0.986	D	0.594	neutral	None	None	None	None	N
R/P	0.9944	likely_pathogenic	0.9934	pathogenic	-1.158	Destabilizing	0.993	D	0.728	prob.delet.	None	None	None	None	N
R/Q	0.2469	likely_benign	0.2096	benign	-1.384	Destabilizing	0.986	D	0.583	neutral	None	None	None	None	N
R/S	0.9545	likely_pathogenic	0.9346	pathogenic	-2.054	Highly Destabilizing	0.939	D	0.624	neutral	N	0.5112089	None	None	N
R/T	0.8098	likely_pathogenic	0.7536	pathogenic	-1.756	Destabilizing	0.982	D	0.725	prob.delet.	N	0.487601321	None	None	N
R/V	0.7249	likely_pathogenic	0.657	pathogenic	-1.158	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
R/W	0.5327	ambiguous	0.4644	ambiguous	-1.265	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
R/Y	0.8075	likely_pathogenic	0.7608	pathogenic	-0.98	Destabilizing	0.998	D	0.748	deleterious	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.