TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19491	58696;58697;58698	chr2:178593829;178593828;178593827	chr2:179458556;179458555;179458554
N2AB	17850	53773;53774;53775	chr2:178593829;178593828;178593827	chr2:179458556;179458555;179458554
N2A	16923	50992;50993;50994	chr2:178593829;178593828;178593827	chr2:179458556;179458555;179458554
N2B	10426	31501;31502;31503	chr2:178593829;178593828;178593827	chr2:179458556;179458555;179458554
Novex-1	10551	31876;31877;31878	chr2:178593829;178593828;178593827	chr2:179458556;179458555;179458554
Novex-2	10618	32077;32078;32079	chr2:178593829;178593828;178593827	chr2:179458556;179458555;179458554
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: Fn3-29
• Domain position: 13
• Structural Position: 14
• Q(SASA): 0.3329
• 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/V	rs2050771375	None	1.0	N	0.7	0.603	0.556695477184	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
E/V	rs2050771375	None	1.0	N	0.7	0.603	0.556695477184	gnomAD-4.0.0	6.57851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.78469E-04

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	0.2837	likely_benign	0.2937	benign	-0.716	Destabilizing	0.999	D	0.662	neutral	N	0.496951523	None	None	N
E/C	0.9162	likely_pathogenic	0.9243	pathogenic	-0.517	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	N
E/D	0.1825	likely_benign	0.1971	benign	-0.973	Destabilizing	0.999	D	0.429	neutral	N	0.473266587	None	None	N
E/F	0.8883	likely_pathogenic	0.9045	pathogenic	-0.069	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/G	0.4172	ambiguous	0.4569	ambiguous	-1.063	Destabilizing	1.0	D	0.655	neutral	N	0.469673718	None	None	N
E/H	0.6758	likely_pathogenic	0.6936	pathogenic	-0.146	Destabilizing	1.0	D	0.59	neutral	None	None	None	None	N
E/I	0.5908	likely_pathogenic	0.6049	pathogenic	0.227	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/K	0.3161	likely_benign	0.3417	ambiguous	-0.563	Destabilizing	0.999	D	0.582	neutral	N	0.484018991	None	None	N
E/L	0.6582	likely_pathogenic	0.6856	pathogenic	0.227	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/M	0.6293	likely_pathogenic	0.6478	pathogenic	0.459	Stabilizing	1.0	D	0.572	neutral	None	None	None	None	N
E/N	0.439	ambiguous	0.4718	ambiguous	-1.085	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/P	0.9887	likely_pathogenic	0.9904	pathogenic	-0.066	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/Q	0.2743	likely_benign	0.2938	benign	-0.936	Destabilizing	1.0	D	0.625	neutral	N	0.488791931	None	None	N
E/R	0.5069	ambiguous	0.5277	ambiguous	-0.167	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/S	0.3584	ambiguous	0.3845	ambiguous	-1.337	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
E/T	0.3649	ambiguous	0.3845	ambiguous	-1.05	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/V	0.3994	ambiguous	0.4075	ambiguous	-0.066	Destabilizing	1.0	D	0.7	prob.neutral	N	0.500148236	None	None	N
E/W	0.967	likely_pathogenic	0.9713	pathogenic	0.188	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/Y	0.8099	likely_pathogenic	0.831	pathogenic	0.172	Stabilizing	1.0	D	0.636	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.