TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33303	100132;100133;100134	chr2:178537202;178537201;178537200	chr2:179401929;179401928;179401927
N2AB	31662	95209;95210;95211	chr2:178537202;178537201;178537200	chr2:179401929;179401928;179401927
N2A	30735	92428;92429;92430	chr2:178537202;178537201;178537200	chr2:179401929;179401928;179401927
N2B	24238	72937;72938;72939	chr2:178537202;178537201;178537200	chr2:179401929;179401928;179401927
Novex-1	24363	73312;73313;73314	chr2:178537202;178537201;178537200	chr2:179401929;179401928;179401927
Novex-2	24430	73513;73514;73515	chr2:178537202;178537201;178537200	chr2:179401929;179401928;179401927
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-130
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.4264
• 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/V	rs746345868	-0.776	0.026	N	0.243	0.106	0.248417906384	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.67112E-04

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	0.5426	ambiguous	0.5021	ambiguous	-1.634	Destabilizing	0.851	D	0.459	neutral	None	None	None	None	N
L/C	0.7196	likely_pathogenic	0.6921	pathogenic	-1.096	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
L/D	0.9506	likely_pathogenic	0.943	pathogenic	-0.801	Destabilizing	0.952	D	0.661	neutral	None	None	None	None	N
L/E	0.7433	likely_pathogenic	0.7308	pathogenic	-0.745	Destabilizing	0.261	N	0.405	neutral	None	None	None	None	N
L/F	0.3468	ambiguous	0.3004	benign	-0.965	Destabilizing	0.976	D	0.532	neutral	None	None	None	None	N
L/G	0.8874	likely_pathogenic	0.8671	pathogenic	-2.01	Highly Destabilizing	0.988	D	0.661	neutral	None	None	None	None	N
L/H	0.6283	likely_pathogenic	0.5804	pathogenic	-1.282	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
L/I	0.1088	likely_benign	0.0954	benign	-0.653	Destabilizing	0.026	N	0.211	neutral	N	0.381007	None	None	N
L/K	0.6003	likely_pathogenic	0.5875	pathogenic	-1.021	Destabilizing	0.976	D	0.547	neutral	None	None	None	None	N
L/M	0.1881	likely_benign	0.1655	benign	-0.637	Destabilizing	0.976	D	0.524	neutral	None	None	None	None	N
L/N	0.7045	likely_pathogenic	0.7072	pathogenic	-0.889	Destabilizing	0.988	D	0.663	neutral	None	None	None	None	N
L/P	0.8827	likely_pathogenic	0.8633	pathogenic	-0.949	Destabilizing	0.995	D	0.663	neutral	N	0.478344333	None	None	N
L/Q	0.4345	ambiguous	0.4051	ambiguous	-0.974	Destabilizing	0.968	D	0.602	neutral	N	0.47672818	None	None	N
L/R	0.5559	ambiguous	0.5161	ambiguous	-0.61	Destabilizing	0.968	D	0.605	neutral	N	0.465529751	None	None	N
L/S	0.6667	likely_pathogenic	0.6126	pathogenic	-1.617	Destabilizing	0.976	D	0.541	neutral	None	None	None	None	N
L/T	0.4218	ambiguous	0.3805	ambiguous	-1.436	Destabilizing	0.919	D	0.496	neutral	None	None	None	None	N
L/V	0.1245	likely_benign	0.1038	benign	-0.949	Destabilizing	0.026	N	0.243	neutral	N	0.356647273	None	None	N
L/W	0.68	likely_pathogenic	0.6185	pathogenic	-1.071	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
L/Y	0.711	likely_pathogenic	0.6571	pathogenic	-0.821	Destabilizing	0.996	D	0.549	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.