TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7373	22342;22343;22344	chr2:178722782;178722781;178722780	chr2:179587509;179587508;179587507
N2AB	7056	21391;21392;21393	chr2:178722782;178722781;178722780	chr2:179587509;179587508;179587507
N2A	6129	18610;18611;18612	chr2:178722782;178722781;178722780	chr2:179587509;179587508;179587507
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-58
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.302
• 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
F/L	None	None	0.015	N	0.256	0.191	0.32471235697	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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
F/A	0.9193	likely_pathogenic	0.9515	pathogenic	-1.915	Destabilizing	0.884	D	0.559	neutral	None	None	None	None	N
F/C	0.7783	likely_pathogenic	0.8531	pathogenic	-0.847	Destabilizing	1.0	D	0.627	neutral	N	0.496657468	None	None	N
F/D	0.9707	likely_pathogenic	0.9845	pathogenic	-0.303	Destabilizing	0.949	D	0.615	neutral	None	None	None	None	N
F/E	0.9725	likely_pathogenic	0.9834	pathogenic	-0.266	Destabilizing	0.918	D	0.615	neutral	None	None	None	None	N
F/G	0.9639	likely_pathogenic	0.9832	pathogenic	-2.209	Highly Destabilizing	0.939	D	0.59	neutral	None	None	None	None	N
F/H	0.8337	likely_pathogenic	0.8831	pathogenic	-0.638	Destabilizing	0.975	D	0.594	neutral	None	None	None	None	N
F/I	0.4968	ambiguous	0.5777	pathogenic	-1.067	Destabilizing	0.853	D	0.435	neutral	N	0.498541539	None	None	N
F/K	0.9568	likely_pathogenic	0.9771	pathogenic	-0.822	Destabilizing	0.939	D	0.617	neutral	None	None	None	None	N
F/L	0.9113	likely_pathogenic	0.9496	pathogenic	-1.067	Destabilizing	0.015	N	0.256	neutral	N	0.495674592	None	None	N
F/M	0.7688	likely_pathogenic	0.8364	pathogenic	-0.746	Destabilizing	0.834	D	0.561	neutral	None	None	None	None	N
F/N	0.9108	likely_pathogenic	0.9418	pathogenic	-0.72	Destabilizing	0.332	N	0.47	neutral	None	None	None	None	N
F/P	0.9973	likely_pathogenic	0.9989	pathogenic	-1.337	Destabilizing	0.996	D	0.643	neutral	None	None	None	None	N
F/Q	0.9324	likely_pathogenic	0.9582	pathogenic	-0.846	Destabilizing	0.988	D	0.647	neutral	None	None	None	None	N
F/R	0.9035	likely_pathogenic	0.945	pathogenic	-0.178	Destabilizing	0.991	D	0.643	neutral	None	None	None	None	N
F/S	0.8392	likely_pathogenic	0.8956	pathogenic	-1.533	Destabilizing	0.521	D	0.449	neutral	N	0.513470919	None	None	N
F/T	0.8764	likely_pathogenic	0.9112	pathogenic	-1.403	Destabilizing	0.332	N	0.453	neutral	None	None	None	None	N
F/V	0.5229	ambiguous	0.6079	pathogenic	-1.337	Destabilizing	0.634	D	0.53	neutral	N	0.497346673	None	None	N
F/W	0.784	likely_pathogenic	0.8395	pathogenic	-0.505	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
F/Y	0.314	likely_benign	0.3606	ambiguous	-0.598	Destabilizing	0.065	N	0.258	neutral	N	0.476299397	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.