TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17871	53836;53837;53838	chr2:178605684;178605683;178605682	chr2:179470411;179470410;179470409
N2AB	16230	48913;48914;48915	chr2:178605684;178605683;178605682	chr2:179470411;179470410;179470409
N2A	15303	46132;46133;46134	chr2:178605684;178605683;178605682	chr2:179470411;179470410;179470409
N2B	8806	26641;26642;26643	chr2:178605684;178605683;178605682	chr2:179470411;179470410;179470409
Novex-1	8931	27016;27017;27018	chr2:178605684;178605683;178605682	chr2:179470411;179470410;179470409
Novex-2	8998	27217;27218;27219	chr2:178605684;178605683;178605682	chr2:179470411;179470410;179470409
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-18
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2122
• 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
Y/C	None	None	1.0	N	0.799	0.254	0.514811571519	gnomAD-4.0.0	6.97927E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.13397E-07	0	0
Y/N	None	None	0.999	N	0.825	0.47	0.70133364227	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
Y/A	0.9571	likely_pathogenic	0.9307	pathogenic	-2.173	Highly Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	N
Y/C	0.7092	likely_pathogenic	0.5826	pathogenic	-1.296	Destabilizing	1.0	D	0.799	deleterious	N	0.474728025	None	None	N
Y/D	0.9888	likely_pathogenic	0.9792	pathogenic	-0.646	Destabilizing	0.999	D	0.839	deleterious	N	0.515747928	None	None	N
Y/E	0.9963	likely_pathogenic	0.9934	pathogenic	-0.529	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/F	0.1742	likely_benign	0.1512	benign	-0.829	Destabilizing	0.994	D	0.587	neutral	N	0.459929144	None	None	N
Y/G	0.9675	likely_pathogenic	0.9486	pathogenic	-2.515	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/H	0.9205	likely_pathogenic	0.879	pathogenic	-0.898	Destabilizing	0.999	D	0.701	prob.neutral	N	0.496892808	None	None	N
Y/I	0.8929	likely_pathogenic	0.8627	pathogenic	-1.13	Destabilizing	0.784	D	0.356	neutral	None	None	None	None	N
Y/K	0.9955	likely_pathogenic	0.992	pathogenic	-1.36	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/L	0.887	likely_pathogenic	0.8531	pathogenic	-1.13	Destabilizing	0.96	D	0.587	neutral	None	None	None	None	N
Y/M	0.9508	likely_pathogenic	0.9287	pathogenic	-0.995	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
Y/N	0.9543	likely_pathogenic	0.923	pathogenic	-1.829	Destabilizing	0.999	D	0.825	deleterious	N	0.471102068	None	None	N
Y/P	0.9785	likely_pathogenic	0.9779	pathogenic	-1.474	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/Q	0.9928	likely_pathogenic	0.9866	pathogenic	-1.633	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Y/R	0.9855	likely_pathogenic	0.9758	pathogenic	-1.039	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/S	0.9173	likely_pathogenic	0.8651	pathogenic	-2.412	Highly Destabilizing	0.999	D	0.799	deleterious	N	0.485425021	None	None	N
Y/T	0.9698	likely_pathogenic	0.9466	pathogenic	-2.187	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
Y/V	0.8028	likely_pathogenic	0.7432	pathogenic	-1.474	Destabilizing	0.983	D	0.595	neutral	None	None	None	None	N
Y/W	0.6672	likely_pathogenic	0.619	pathogenic	-0.399	Destabilizing	1.0	D	0.673	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.