TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21140	63643;63644;63645	chr2:178587989;178587988;178587987	chr2:179452716;179452715;179452714
N2AB	19499	58720;58721;58722	chr2:178587989;178587988;178587987	chr2:179452716;179452715;179452714
N2A	18572	55939;55940;55941	chr2:178587989;178587988;178587987	chr2:179452716;179452715;179452714
N2B	12075	36448;36449;36450	chr2:178587989;178587988;178587987	chr2:179452716;179452715;179452714
Novex-1	12200	36823;36824;36825	chr2:178587989;178587988;178587987	chr2:179452716;179452715;179452714
Novex-2	12267	37024;37025;37026	chr2:178587989;178587988;178587987	chr2:179452716;179452715;179452714
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-41
• Domain position: 77
• Structural Position: 103
• Q(SASA): 0.1981
• 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/K	rs765307639	None	0.885	D	0.495	0.28	0.347659731818	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs765307639	None	0.885	D	0.495	0.28	0.347659731818	gnomAD-4.0.0	1.86058E-06	None	None	None	None	N	None	1.33579E-05	0	None	0	0	None	0	0	1.696E-06	0	0
E/Q	rs765307639	-1.191	0.322	N	0.34	0.169	0.207176502487	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.66E-05	None	0	None	0	0	0
E/Q	rs765307639	-1.191	0.322	N	0.34	0.169	0.207176502487	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94175E-04	None	0	0	0	0	0
E/Q	rs765307639	-1.191	0.322	N	0.34	0.169	0.207176502487	gnomAD-4.0.0	1.86058E-06	None	None	None	None	N	None	0	0	None	0	6.73098E-05	None	0	0	0	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	0.1141	likely_benign	0.1255	benign	-0.954	Destabilizing	0.939	D	0.533	neutral	N	0.473561285	None	None	N
E/C	0.7274	likely_pathogenic	0.751	pathogenic	-0.595	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
E/D	0.1806	likely_benign	0.174	benign	-1.318	Destabilizing	0.939	D	0.483	neutral	N	0.520540459	None	None	N
E/F	0.64	likely_pathogenic	0.6507	pathogenic	-0.273	Destabilizing	0.986	D	0.812	deleterious	None	None	None	None	N
E/G	0.1864	likely_benign	0.196	benign	-1.367	Destabilizing	0.982	D	0.705	prob.neutral	N	0.477284268	None	None	N
E/H	0.5049	ambiguous	0.5106	ambiguous	-0.607	Destabilizing	0.998	D	0.638	neutral	None	None	None	None	N
E/I	0.21	likely_benign	0.2256	benign	0.191	Stabilizing	0.973	D	0.769	deleterious	None	None	None	None	N
E/K	0.2199	likely_benign	0.2217	benign	-1.016	Destabilizing	0.885	D	0.495	neutral	D	0.522193898	None	None	N
E/L	0.2163	likely_benign	0.2387	benign	0.191	Stabilizing	0.128	N	0.499	neutral	None	None	None	None	N
E/M	0.2818	likely_benign	0.304	benign	0.742	Stabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
E/N	0.2905	likely_benign	0.2965	benign	-1.489	Destabilizing	0.986	D	0.624	neutral	None	None	None	None	N
E/P	0.3162	likely_benign	0.3083	benign	-0.17	Destabilizing	0.993	D	0.752	deleterious	None	None	None	None	N
E/Q	0.1576	likely_benign	0.1648	benign	-1.301	Destabilizing	0.322	N	0.34	neutral	N	0.513998489	None	None	N
E/R	0.352	ambiguous	0.3472	ambiguous	-0.699	Destabilizing	0.973	D	0.622	neutral	None	None	None	None	N
E/S	0.2028	likely_benign	0.2064	benign	-1.887	Destabilizing	0.953	D	0.523	neutral	None	None	None	None	N
E/T	0.1689	likely_benign	0.1771	benign	-1.542	Destabilizing	0.986	D	0.707	prob.neutral	None	None	None	None	N
E/V	0.1299	likely_benign	0.1445	benign	-0.17	Destabilizing	0.885	D	0.654	neutral	N	0.485486523	None	None	N
E/W	0.8253	likely_pathogenic	0.8156	pathogenic	-0.052	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
E/Y	0.5534	ambiguous	0.5466	ambiguous	-0.04	Destabilizing	0.993	D	0.786	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.