TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33078	99457;99458;99459	chr2:178538597;178538596;178538595	chr2:179403324;179403323;179403322
N2AB	31437	94534;94535;94536	chr2:178538597;178538596;178538595	chr2:179403324;179403323;179403322
N2A	30510	91753;91754;91755	chr2:178538597;178538596;178538595	chr2:179403324;179403323;179403322
N2B	24013	72262;72263;72264	chr2:178538597;178538596;178538595	chr2:179403324;179403323;179403322
Novex-1	24138	72637;72638;72639	chr2:178538597;178538596;178538595	chr2:179403324;179403323;179403322
Novex-2	24205	72838;72839;72840	chr2:178538597;178538596;178538595	chr2:179403324;179403323;179403322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-129
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5309
• 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
E/K	rs771047688	0.716	0.885	N	0.454	0.249	0.272205846399	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/K	rs771047688	0.716	0.885	N	0.454	0.249	0.272205846399	gnomAD-4.0.0	1.59165E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85892E-06	0	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
E/A	0.1855	likely_benign	0.2207	benign	-0.213	Destabilizing	0.939	D	0.511	neutral	N	0.45040837	None	None	I
E/C	0.9225	likely_pathogenic	0.9385	pathogenic	0.034	Stabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
E/D	0.1549	likely_benign	0.1883	benign	-0.257	Destabilizing	0.939	D	0.415	neutral	N	0.459182569	None	None	I
E/F	0.9051	likely_pathogenic	0.9265	pathogenic	-0.147	Destabilizing	0.993	D	0.609	neutral	None	None	None	None	I
E/G	0.228	likely_benign	0.2731	benign	-0.384	Destabilizing	0.982	D	0.469	neutral	N	0.475589242	None	None	I
E/H	0.6608	likely_pathogenic	0.7225	pathogenic	0.18	Stabilizing	0.998	D	0.371	neutral	None	None	None	None	I
E/I	0.5194	ambiguous	0.5772	pathogenic	0.194	Stabilizing	0.973	D	0.539	neutral	None	None	None	None	I
E/K	0.2137	likely_benign	0.258	benign	0.486	Stabilizing	0.885	D	0.454	neutral	N	0.483790225	None	None	I
E/L	0.5931	likely_pathogenic	0.6666	pathogenic	0.194	Stabilizing	0.91	D	0.552	neutral	None	None	None	None	I
E/M	0.6477	likely_pathogenic	0.706	pathogenic	0.215	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	I
E/N	0.3775	ambiguous	0.4608	ambiguous	0.156	Stabilizing	0.986	D	0.387	neutral	None	None	None	None	I
E/P	0.6132	likely_pathogenic	0.6782	pathogenic	0.078	Stabilizing	0.993	D	0.468	neutral	None	None	None	None	I
E/Q	0.2029	likely_benign	0.2433	benign	0.198	Stabilizing	0.322	N	0.363	neutral	N	0.508648597	None	None	I
E/R	0.3861	ambiguous	0.4521	ambiguous	0.655	Stabilizing	0.973	D	0.385	neutral	None	None	None	None	I
E/S	0.2584	likely_benign	0.3119	benign	0.024	Stabilizing	0.953	D	0.443	neutral	None	None	None	None	I
E/T	0.3315	likely_benign	0.395	ambiguous	0.171	Stabilizing	0.953	D	0.471	neutral	None	None	None	None	I
E/V	0.3352	likely_benign	0.3836	ambiguous	0.078	Stabilizing	0.322	N	0.488	neutral	N	0.466436615	None	None	I
E/W	0.9672	likely_pathogenic	0.9768	pathogenic	-0.035	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
E/Y	0.8254	likely_pathogenic	0.865	pathogenic	0.093	Stabilizing	0.998	D	0.575	neutral	None	None	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.