TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3293	10102;10103;10104	chr2:178764638;178764637;178764636	chr2:179629365;179629364;179629363
N2AB	3293	10102;10103;10104	chr2:178764638;178764637;178764636	chr2:179629365;179629364;179629363
N2A	3293	10102;10103;10104	chr2:178764638;178764637;178764636	chr2:179629365;179629364;179629363
N2B	3247	9964;9965;9966	chr2:178764638;178764637;178764636	chr2:179629365;179629364;179629363
Novex-1	3247	9964;9965;9966	chr2:178764638;178764637;178764636	chr2:179629365;179629364;179629363
Novex-2	3247	9964;9965;9966	chr2:178764638;178764637;178764636	chr2:179629365;179629364;179629363
Novex-3	3293	10102;10103;10104	chr2:178764638;178764637;178764636	chr2:179629365;179629364;179629363

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-23
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.6085
• 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
E/D	rs4894043	None	0.989	N	0.485	0.327	0.330331372229	gnomAD-4.0.0	6.84068E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65579E-05
E/Q	rs2090028411	None	0.889	N	0.31	0.257	0.291694819147	gnomAD-4.0.0	2.73628E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59718E-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	0.2961	likely_benign	0.4624	ambiguous	-0.925	Destabilizing	0.978	D	0.587	neutral	N	0.502007638	None	None	N
E/C	0.9523	likely_pathogenic	0.975	pathogenic	-0.403	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/D	0.4342	ambiguous	0.555	ambiguous	-1.116	Destabilizing	0.989	D	0.485	neutral	N	0.511338012	None	None	N
E/F	0.9246	likely_pathogenic	0.9624	pathogenic	-0.713	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/G	0.4776	ambiguous	0.6409	pathogenic	-1.258	Destabilizing	0.989	D	0.644	neutral	N	0.510603052	None	None	N
E/H	0.7536	likely_pathogenic	0.8671	pathogenic	-1.055	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
E/I	0.5897	likely_pathogenic	0.7453	pathogenic	-0.027	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
E/K	0.367	ambiguous	0.6074	pathogenic	-0.596	Destabilizing	0.978	D	0.526	neutral	N	0.505072118	None	None	N
E/L	0.6831	likely_pathogenic	0.8311	pathogenic	-0.027	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
E/M	0.6648	likely_pathogenic	0.815	pathogenic	0.507	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/N	0.5379	ambiguous	0.7047	pathogenic	-0.95	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
E/P	0.9867	likely_pathogenic	0.993	pathogenic	-0.305	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
E/Q	0.2198	likely_benign	0.3633	ambiguous	-0.85	Destabilizing	0.889	D	0.31	neutral	N	0.503721528	None	None	N
E/R	0.5327	ambiguous	0.7299	pathogenic	-0.464	Destabilizing	0.998	D	0.616	neutral	None	None	None	None	N
E/S	0.4562	ambiguous	0.6246	pathogenic	-1.264	Destabilizing	0.82	D	0.387	neutral	None	None	None	None	N
E/T	0.3892	ambiguous	0.5719	pathogenic	-0.987	Destabilizing	0.983	D	0.647	neutral	None	None	None	None	N
E/V	0.363	ambiguous	0.5291	ambiguous	-0.305	Destabilizing	0.998	D	0.652	neutral	N	0.498054494	None	None	N
E/W	0.9819	likely_pathogenic	0.9917	pathogenic	-0.551	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/Y	0.8556	likely_pathogenic	0.9237	pathogenic	-0.478	Destabilizing	1.0	D	0.743	deleterious	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.