TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26631	80116;80117;80118	chr2:178566241;178566240;178566239	chr2:179430968;179430967;179430966
N2AB	24990	75193;75194;75195	chr2:178566241;178566240;178566239	chr2:179430968;179430967;179430966
N2A	24063	72412;72413;72414	chr2:178566241;178566240;178566239	chr2:179430968;179430967;179430966
N2B	17566	52921;52922;52923	chr2:178566241;178566240;178566239	chr2:179430968;179430967;179430966
Novex-1	17691	53296;53297;53298	chr2:178566241;178566240;178566239	chr2:179430968;179430967;179430966
Novex-2	17758	53497;53498;53499	chr2:178566241;178566240;178566239	chr2:179430968;179430967;179430966
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-138
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.4128
• 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
G/R	None	None	0.056	N	0.352	0.309	0.451882325854	gnomAD-4.0.0	1.59145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85868E-06	0	0
G/S	rs1705788431	None	0.805	N	0.445	0.207	0.200317383148	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
G/S	rs1705788431	None	0.805	N	0.445	0.207	0.200317383148	gnomAD-4.0.0	2.56255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39339E-06	0	2.84527E-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
G/A	0.1477	likely_benign	0.1519	benign	-0.307	Destabilizing	0.204	N	0.31	neutral	N	0.499674902	None	None	N
G/C	0.2555	likely_benign	0.2528	benign	-0.953	Destabilizing	0.999	D	0.665	neutral	D	0.528497885	None	None	N
G/D	0.2265	likely_benign	0.2271	benign	-0.7	Destabilizing	0.935	D	0.501	neutral	N	0.512124125	None	None	N
G/E	0.2202	likely_benign	0.2199	benign	-0.863	Destabilizing	0.975	D	0.527	neutral	None	None	None	None	N
G/F	0.624	likely_pathogenic	0.6236	pathogenic	-1.042	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
G/H	0.4472	ambiguous	0.4557	ambiguous	-0.484	Destabilizing	0.997	D	0.617	neutral	None	None	None	None	N
G/I	0.3179	likely_benign	0.3136	benign	-0.501	Destabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	N
G/K	0.3886	ambiguous	0.3906	ambiguous	-0.868	Destabilizing	0.845	D	0.505	neutral	None	None	None	None	N
G/L	0.4674	ambiguous	0.4757	ambiguous	-0.501	Destabilizing	0.975	D	0.627	neutral	None	None	None	None	N
G/M	0.4436	ambiguous	0.4462	ambiguous	-0.641	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
G/N	0.26	likely_benign	0.2656	benign	-0.52	Destabilizing	0.253	N	0.322	neutral	None	None	None	None	N
G/P	0.8355	likely_pathogenic	0.8414	pathogenic	-0.407	Destabilizing	0.987	D	0.6	neutral	None	None	None	None	N
G/Q	0.3582	ambiguous	0.3646	ambiguous	-0.807	Destabilizing	0.975	D	0.599	neutral	None	None	None	None	N
G/R	0.3336	likely_benign	0.3349	benign	-0.405	Destabilizing	0.056	N	0.352	neutral	N	0.519684815	None	None	N
G/S	0.1197	likely_benign	0.1262	benign	-0.632	Destabilizing	0.805	D	0.445	neutral	N	0.483167433	None	None	N
G/T	0.1642	likely_benign	0.1637	benign	-0.731	Destabilizing	0.975	D	0.526	neutral	None	None	None	None	N
G/V	0.2179	likely_benign	0.2139	benign	-0.407	Destabilizing	0.967	D	0.655	neutral	N	0.507718382	None	None	N
G/W	0.4867	ambiguous	0.4752	ambiguous	-1.174	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
G/Y	0.4651	ambiguous	0.4609	ambiguous	-0.849	Destabilizing	0.999	D	0.673	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.