TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28458	85597;85598;85599	chr2:178560760;178560759;178560758	chr2:179425487;179425486;179425485
N2AB	26817	80674;80675;80676	chr2:178560760;178560759;178560758	chr2:179425487;179425486;179425485
N2A	25890	77893;77894;77895	chr2:178560760;178560759;178560758	chr2:179425487;179425486;179425485
N2B	19393	58402;58403;58404	chr2:178560760;178560759;178560758	chr2:179425487;179425486;179425485
Novex-1	19518	58777;58778;58779	chr2:178560760;178560759;178560758	chr2:179425487;179425486;179425485
Novex-2	19585	58978;58979;58980	chr2:178560760;178560759;178560758	chr2:179425487;179425486;179425485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-95
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.1204
• 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
L/P	rs776361284	-1.94	0.994	N	0.872	0.516	0.805270340984	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	4.14E-05	0	None	0	5.15E-05	None	0	None	0	0	0
L/P	rs776361284	-1.94	0.994	N	0.872	0.516	0.805270340984	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs776361284	-1.94	0.994	N	0.872	0.516	0.805270340984	gnomAD-4.0.0	3.09861E-06	None	None	None	None	N	None	2.66973E-05	0	None	0	4.46409E-05	None	0	0	0	0	1.60123E-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
L/A	0.7875	likely_pathogenic	0.8061	pathogenic	-2.216	Highly Destabilizing	0.916	D	0.719	prob.delet.	None	None	None	None	N
L/C	0.8748	likely_pathogenic	0.8819	pathogenic	-1.587	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
L/D	0.9961	likely_pathogenic	0.9964	pathogenic	-2.332	Highly Destabilizing	0.996	D	0.872	deleterious	None	None	None	None	N
L/E	0.9749	likely_pathogenic	0.9784	pathogenic	-2.099	Highly Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	N
L/F	0.4821	ambiguous	0.439	ambiguous	-1.226	Destabilizing	0.967	D	0.821	deleterious	N	0.499020417	None	None	N
L/G	0.9692	likely_pathogenic	0.9712	pathogenic	-2.768	Highly Destabilizing	0.987	D	0.847	deleterious	None	None	None	None	N
L/H	0.9656	likely_pathogenic	0.9696	pathogenic	-2.314	Highly Destabilizing	0.999	D	0.849	deleterious	N	0.517671331	None	None	N
L/I	0.1211	likely_benign	0.1147	benign	-0.63	Destabilizing	0.056	N	0.42	neutral	N	0.469735997	None	None	N
L/K	0.956	likely_pathogenic	0.9662	pathogenic	-1.59	Destabilizing	0.987	D	0.824	deleterious	None	None	None	None	N
L/M	0.2284	likely_benign	0.218	benign	-0.729	Destabilizing	0.693	D	0.644	neutral	None	None	None	None	N
L/N	0.9827	likely_pathogenic	0.9842	pathogenic	-1.92	Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
L/P	0.8147	likely_pathogenic	0.8437	pathogenic	-1.138	Destabilizing	0.994	D	0.872	deleterious	N	0.509947824	None	None	N
L/Q	0.9314	likely_pathogenic	0.9431	pathogenic	-1.744	Destabilizing	0.987	D	0.853	deleterious	None	None	None	None	N
L/R	0.9313	likely_pathogenic	0.9452	pathogenic	-1.456	Destabilizing	0.983	D	0.839	deleterious	D	0.522444271	None	None	N
L/S	0.9531	likely_pathogenic	0.959	pathogenic	-2.635	Highly Destabilizing	0.987	D	0.821	deleterious	None	None	None	None	N
L/T	0.8093	likely_pathogenic	0.8235	pathogenic	-2.251	Highly Destabilizing	0.975	D	0.777	deleterious	None	None	None	None	N
L/V	0.1388	likely_benign	0.1331	benign	-1.138	Destabilizing	0.369	N	0.745	deleterious	N	0.468519702	None	None	N
L/W	0.8714	likely_pathogenic	0.8577	pathogenic	-1.611	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
L/Y	0.9306	likely_pathogenic	0.9294	pathogenic	-1.279	Destabilizing	0.987	D	0.791	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.