TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18689	56290;56291;56292	chr2:178599836;178599835;178599834	chr2:179464563;179464562;179464561
N2AB	17048	51367;51368;51369	chr2:178599836;178599835;178599834	chr2:179464563;179464562;179464561
N2A	16121	48586;48587;48588	chr2:178599836;178599835;178599834	chr2:179464563;179464562;179464561
N2B	9624	29095;29096;29097	chr2:178599836;178599835;178599834	chr2:179464563;179464562;179464561
Novex-1	9749	29470;29471;29472	chr2:178599836;178599835;178599834	chr2:179464563;179464562;179464561
Novex-2	9816	29671;29672;29673	chr2:178599836;178599835;178599834	chr2:179464563;179464562;179464561
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-116
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5262
• 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
D/N	rs763814390	0.034	0.117	N	0.327	0.145	0.242825505644	gnomAD-2.1.1	1.34E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	5.65185E-04
D/N	rs763814390	0.034	0.117	N	0.327	0.145	0.242825505644	gnomAD-4.0.0	8.31067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	9.93049E-04	0	0	3.13716E-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
D/A	0.1249	likely_benign	0.1163	benign	-0.027	Destabilizing	0.062	N	0.293	neutral	N	0.512331981	None	None	N
D/C	0.4985	ambiguous	0.4427	ambiguous	-0.112	Destabilizing	0.935	D	0.392	neutral	None	None	None	None	N
D/E	0.0828	likely_benign	0.0761	benign	-0.316	Destabilizing	None	N	0.15	neutral	N	0.405913805	None	None	N
D/F	0.4106	ambiguous	0.3527	ambiguous	0.225	Stabilizing	0.38	N	0.361	neutral	None	None	None	None	N
D/G	0.2155	likely_benign	0.1987	benign	-0.253	Destabilizing	0.117	N	0.287	neutral	N	0.512852056	None	None	N
D/H	0.1976	likely_benign	0.1789	benign	0.553	Stabilizing	0.484	N	0.309	neutral	N	0.513372131	None	None	N
D/I	0.1499	likely_benign	0.1277	benign	0.522	Stabilizing	0.235	N	0.361	neutral	None	None	None	None	N
D/K	0.2549	likely_benign	0.2347	benign	0.41	Stabilizing	0.081	N	0.29	neutral	None	None	None	None	N
D/L	0.1922	likely_benign	0.1749	benign	0.522	Stabilizing	0.001	N	0.276	neutral	None	None	None	None	N
D/M	0.342	ambiguous	0.3045	benign	0.387	Stabilizing	0.38	N	0.361	neutral	None	None	None	None	N
D/N	0.0955	likely_benign	0.091	benign	-0.099	Destabilizing	0.117	N	0.327	neutral	N	0.482875866	None	None	N
D/P	0.8318	likely_pathogenic	0.7891	pathogenic	0.363	Stabilizing	0.555	D	0.325	neutral	None	None	None	None	N
D/Q	0.1925	likely_benign	0.1728	benign	-0.017	Destabilizing	0.016	N	0.162	neutral	None	None	None	None	N
D/R	0.3269	likely_benign	0.2924	benign	0.696	Stabilizing	0.235	N	0.341	neutral	None	None	None	None	N
D/S	0.1049	likely_benign	0.0975	benign	-0.176	Destabilizing	0.081	N	0.237	neutral	None	None	None	None	N
D/T	0.1267	likely_benign	0.1199	benign	0.014	Stabilizing	0.149	N	0.332	neutral	None	None	None	None	N
D/V	0.0981	likely_benign	0.0901	benign	0.363	Stabilizing	0.062	N	0.336	neutral	N	0.513198773	None	None	N
D/W	0.7834	likely_pathogenic	0.7275	pathogenic	0.365	Stabilizing	0.935	D	0.462	neutral	None	None	None	None	N
D/Y	0.1864	likely_benign	0.1734	benign	0.481	Stabilizing	0.741	D	0.361	neutral	N	0.513718848	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.