TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17354	52285;52286;52287	chr2:178609250;178609249;178609248	chr2:179473977;179473976;179473975
N2AB	15713	47362;47363;47364	chr2:178609250;178609249;178609248	chr2:179473977;179473976;179473975
N2A	14786	44581;44582;44583	chr2:178609250;178609249;178609248	chr2:179473977;179473976;179473975
N2B	8289	25090;25091;25092	chr2:178609250;178609249;178609248	chr2:179473977;179473976;179473975
Novex-1	8414	25465;25466;25467	chr2:178609250;178609249;178609248	chr2:179473977;179473976;179473975
Novex-2	8481	25666;25667;25668	chr2:178609250;178609249;178609248	chr2:179473977;179473976;179473975
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-112
• Domain position: 104
• Structural Position: 162
• Q(SASA): 0.9015
• Predicted PPI site: I

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/E	rs886055269	None	0.051	N	0.272	0.06	0.252162846088	gnomAD-4.0.0	3.64904E-06	None	None	None	None	I	None	0	3.25267E-05	None	0	0	None	0	0	0	1.86164E-05	0
D/V	rs397517606	0.267	0.669	N	0.369	0.292	0.521015664611	gnomAD-2.1.1	5.44E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.12E-05	0
D/Y	None	None	0.966	N	0.345	0.325	0.642701035604	gnomAD-4.0.0	1.82058E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.85625E-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
D/A	0.1541	likely_benign	0.1395	benign	-0.071	Destabilizing	0.051	N	0.199	neutral	N	0.465621044	None	None	I
D/C	0.626	likely_pathogenic	0.5828	pathogenic	0.048	Stabilizing	0.998	D	0.341	neutral	None	None	None	None	I
D/E	0.2096	likely_benign	0.1822	benign	-0.14	Destabilizing	0.051	N	0.272	neutral	N	0.464887538	None	None	I
D/F	0.6311	likely_pathogenic	0.5852	pathogenic	-0.22	Destabilizing	0.949	D	0.349	neutral	None	None	None	None	I
D/G	0.2058	likely_benign	0.1814	benign	-0.207	Destabilizing	0.454	N	0.33	neutral	N	0.491634209	None	None	I
D/H	0.2916	likely_benign	0.2675	benign	0.163	Stabilizing	0.966	D	0.356	neutral	N	0.487440757	None	None	I
D/I	0.3081	likely_benign	0.287	benign	0.221	Stabilizing	0.728	D	0.337	neutral	None	None	None	None	I
D/K	0.3248	likely_benign	0.2926	benign	0.317	Stabilizing	0.842	D	0.345	neutral	None	None	None	None	I
D/L	0.3799	ambiguous	0.3487	ambiguous	0.221	Stabilizing	0.016	N	0.305	neutral	None	None	None	None	I
D/M	0.6007	likely_pathogenic	0.5663	pathogenic	0.183	Stabilizing	0.949	D	0.337	neutral	None	None	None	None	I
D/N	0.1096	likely_benign	0.0986	benign	0.298	Stabilizing	0.051	N	0.338	neutral	D	0.525304066	None	None	I
D/P	0.5488	ambiguous	0.5292	ambiguous	0.144	Stabilizing	0.974	D	0.355	neutral	None	None	None	None	I
D/Q	0.3339	likely_benign	0.3081	benign	0.288	Stabilizing	0.949	D	0.316	neutral	None	None	None	None	I
D/R	0.3418	ambiguous	0.3116	benign	0.504	Stabilizing	0.949	D	0.373	neutral	None	None	None	None	I
D/S	0.119	likely_benign	0.1085	benign	0.131	Stabilizing	0.525	D	0.315	neutral	None	None	None	None	I
D/T	0.189	likely_benign	0.1804	benign	0.228	Stabilizing	0.067	N	0.243	neutral	None	None	None	None	I
D/V	0.2059	likely_benign	0.1923	benign	0.144	Stabilizing	0.669	D	0.369	neutral	N	0.501043126	None	None	I
D/W	0.9058	likely_pathogenic	0.8899	pathogenic	-0.187	Destabilizing	0.998	D	0.403	neutral	None	None	None	None	I
D/Y	0.2738	likely_benign	0.2491	benign	-0.003	Destabilizing	0.966	D	0.345	neutral	N	0.499215136	None	None	I

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.