TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21978	66157;66158;66159	chr2:178582524;178582523;178582522	chr2:179447251;179447250;179447249
N2AB	20337	61234;61235;61236	chr2:178582524;178582523;178582522	chr2:179447251;179447250;179447249
N2A	19410	58453;58454;58455	chr2:178582524;178582523;178582522	chr2:179447251;179447250;179447249
N2B	12913	38962;38963;38964	chr2:178582524;178582523;178582522	chr2:179447251;179447250;179447249
Novex-1	13038	39337;39338;39339	chr2:178582524;178582523;178582522	chr2:179447251;179447250;179447249
Novex-2	13105	39538;39539;39540	chr2:178582524;178582523;178582522	chr2:179447251;179447250;179447249
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: Fn3-47
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4498
• 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	None	None	0.014	N	0.277	0.262	0.180583059064	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1901	likely_benign	0.1764	benign	-0.697	Destabilizing	0.698	D	0.581	neutral	N	0.507592591	None	None	N
E/C	0.8575	likely_pathogenic	0.8174	pathogenic	-0.152	Destabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
E/D	0.1411	likely_benign	0.1278	benign	-0.713	Destabilizing	0.006	N	0.119	neutral	N	0.49972247	None	None	N
E/F	0.7805	likely_pathogenic	0.7413	pathogenic	-0.549	Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N
E/G	0.2391	likely_benign	0.2163	benign	-0.968	Destabilizing	0.822	D	0.611	neutral	D	0.522831403	None	None	N
E/H	0.5614	ambiguous	0.4994	ambiguous	-0.691	Destabilizing	0.978	D	0.585	neutral	None	None	None	None	N
E/I	0.3728	ambiguous	0.3622	ambiguous	0.011	Stabilizing	0.978	D	0.759	deleterious	None	None	None	None	N
E/K	0.257	likely_benign	0.2246	benign	-0.201	Destabilizing	0.014	N	0.277	neutral	N	0.428379659	None	None	N
E/L	0.3485	ambiguous	0.3198	benign	0.011	Stabilizing	0.956	D	0.681	prob.neutral	None	None	None	None	N
E/M	0.429	ambiguous	0.4069	ambiguous	0.393	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
E/N	0.2401	likely_benign	0.2112	benign	-0.476	Destabilizing	0.754	D	0.538	neutral	None	None	None	None	N
E/P	0.9576	likely_pathogenic	0.9203	pathogenic	-0.204	Destabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
E/Q	0.1553	likely_benign	0.1444	benign	-0.421	Destabilizing	0.822	D	0.551	neutral	N	0.512921053	None	None	N
E/R	0.4409	ambiguous	0.3856	ambiguous	-0.016	Destabilizing	0.915	D	0.565	neutral	None	None	None	None	N
E/S	0.2215	likely_benign	0.2046	benign	-0.715	Destabilizing	0.193	N	0.274	neutral	None	None	None	None	N
E/T	0.2353	likely_benign	0.2255	benign	-0.502	Destabilizing	0.754	D	0.629	neutral	None	None	None	None	N
E/V	0.2393	likely_benign	0.2262	benign	-0.204	Destabilizing	0.942	D	0.7	prob.neutral	N	0.470131471	None	None	N
E/W	0.9446	likely_pathogenic	0.926	pathogenic	-0.387	Destabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
E/Y	0.6845	likely_pathogenic	0.6253	pathogenic	-0.319	Destabilizing	0.993	D	0.757	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.