TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4634	14125;14126;14127	chr2:178739333;178739332;178739331	chr2:179604060;179604059;179604058
N2AB	4317	13174;13175;13176	chr2:178739333;178739332;178739331	chr2:179604060;179604059;179604058
N2A	None	None	chr2:None	chr2:None
N2B	4271	13036;13037;13038	chr2:178739333;178739332;178739331	chr2:179604060;179604059;179604058
Novex-1	4396	13411;13412;13413	chr2:178739333;178739332;178739331	chr2:179604060;179604059;179604058
Novex-2	4463	13612;13613;13614	chr2:178739333;178739332;178739331	chr2:179604060;179604059;179604058
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: Ig-29
• Domain position: 29
• Structural Position: 45
• Q(SASA): 0.4617
• 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	rs1408608016	-0.516	0.117	N	0.42	0.056	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/D	rs1408608016	-0.516	0.117	N	0.42	0.056	None	gnomAD-4.0.0	4.10548E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39686E-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	0.1293	likely_benign	0.1338	benign	-0.492	Destabilizing	0.027	N	0.449	neutral	N	0.510704917	None	None	N
E/C	0.7706	likely_pathogenic	0.7868	pathogenic	-0.24	Destabilizing	0.824	D	0.543	neutral	None	None	None	None	N
E/D	0.1547	likely_benign	0.1724	benign	-0.463	Destabilizing	0.117	N	0.42	neutral	N	0.514528051	None	None	N
E/F	0.6058	likely_pathogenic	0.657	pathogenic	-0.21	Destabilizing	0.38	N	0.584	neutral	None	None	None	None	N
E/G	0.1742	likely_benign	0.1894	benign	-0.727	Destabilizing	0.117	N	0.549	neutral	D	0.613103284	None	None	N
E/H	0.3345	likely_benign	0.3776	ambiguous	0.023	Stabilizing	0.555	D	0.507	neutral	None	None	None	None	N
E/I	0.2297	likely_benign	0.2382	benign	0.109	Stabilizing	0.001	N	0.386	neutral	None	None	None	None	N
E/K	0.1001	likely_benign	0.1015	benign	0.061	Stabilizing	0.001	N	0.115	neutral	N	0.49114849	None	None	N
E/L	0.3101	likely_benign	0.3337	benign	0.109	Stabilizing	0.035	N	0.47	neutral	None	None	None	None	N
E/M	0.3089	likely_benign	0.3311	benign	0.167	Stabilizing	0.38	N	0.565	neutral	None	None	None	None	N
E/N	0.2067	likely_benign	0.24	benign	-0.303	Destabilizing	0.149	N	0.472	neutral	None	None	None	None	N
E/P	0.835	likely_pathogenic	0.8774	pathogenic	-0.071	Destabilizing	0.555	D	0.593	neutral	None	None	None	None	N
E/Q	0.1161	likely_benign	0.1245	benign	-0.246	Destabilizing	0.005	N	0.229	neutral	N	0.512905805	None	None	N
E/R	0.1756	likely_benign	0.187	benign	0.387	Stabilizing	0.081	N	0.415	neutral	None	None	None	None	N
E/S	0.177	likely_benign	0.1984	benign	-0.496	Destabilizing	0.149	N	0.428	neutral	None	None	None	None	N
E/T	0.1486	likely_benign	0.1611	benign	-0.306	Destabilizing	0.081	N	0.511	neutral	None	None	None	None	N
E/V	0.1386	likely_benign	0.1393	benign	-0.071	Destabilizing	None	N	0.319	neutral	D	0.539019985	None	None	N
E/W	0.7951	likely_pathogenic	0.8328	pathogenic	-0.012	Destabilizing	0.935	D	0.571	neutral	None	None	None	None	N
E/Y	0.4615	ambiguous	0.4989	ambiguous	0.037	Stabilizing	0.555	D	0.593	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.