TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31832	95719;95720;95721	chr2:178545616;178545615;178545614	chr2:179410343;179410342;179410341
N2AB	30191	90796;90797;90798	chr2:178545616;178545615;178545614	chr2:179410343;179410342;179410341
N2A	29264	88015;88016;88017	chr2:178545616;178545615;178545614	chr2:179410343;179410342;179410341
N2B	22767	68524;68525;68526	chr2:178545616;178545615;178545614	chr2:179410343;179410342;179410341
Novex-1	22892	68899;68900;68901	chr2:178545616;178545615;178545614	chr2:179410343;179410342;179410341
Novex-2	22959	69100;69101;69102	chr2:178545616;178545615;178545614	chr2:179410343;179410342;179410341
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: Fn3-120
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8898
• Predicted PPI site: I

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/A	None	None	0.645	N	0.526	0.346	0.31291088546	gnomAD-4.0.0	1.36847E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79903E-06	0	0
E/K	rs753982218	0.764	0.645	N	0.559	0.279	0.32082282376	gnomAD-2.1.1	8.03E-06	None	None	None	None	I	None	0	5.79E-05	None	0	0	None	0	None	0	0	0
E/K	rs753982218	0.764	0.645	N	0.559	0.279	0.32082282376	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/K	rs753982218	0.764	0.645	N	0.559	0.279	0.32082282376	gnomAD-4.0.0	6.40579E-06	None	None	None	None	I	None	0	8.47371E-05	None	0	0	None	0	0	0	0	0
E/V	None	None	0.928	N	0.568	0.47	0.476908202251	gnomAD-4.0.0	6.84233E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99517E-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	0.1083	likely_benign	0.0966	benign	-0.025	Destabilizing	0.645	D	0.526	neutral	N	0.448216214	None	None	I
E/C	0.7277	likely_pathogenic	0.6988	pathogenic	-0.003	Destabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	I
E/D	0.1025	likely_benign	0.1013	benign	-0.278	Destabilizing	0.002	N	0.307	neutral	N	0.473690662	None	None	I
E/F	0.6213	likely_pathogenic	0.5662	pathogenic	-0.106	Destabilizing	0.995	D	0.63	neutral	None	None	None	None	I
E/G	0.1513	likely_benign	0.1337	benign	-0.136	Destabilizing	0.645	D	0.439	neutral	N	0.519983099	None	None	I
E/H	0.3695	ambiguous	0.3421	ambiguous	0.386	Stabilizing	0.995	D	0.587	neutral	None	None	None	None	I
E/I	0.2109	likely_benign	0.1812	benign	0.208	Stabilizing	0.945	D	0.646	neutral	None	None	None	None	I
E/K	0.1235	likely_benign	0.1113	benign	0.536	Stabilizing	0.645	D	0.559	neutral	N	0.496546092	None	None	I
E/L	0.2449	likely_benign	0.2084	benign	0.208	Stabilizing	0.945	D	0.634	neutral	None	None	None	None	I
E/M	0.3402	ambiguous	0.3001	benign	0.098	Stabilizing	0.995	D	0.592	neutral	None	None	None	None	I
E/N	0.2076	likely_benign	0.1904	benign	0.312	Stabilizing	0.809	D	0.533	neutral	None	None	None	None	I
E/P	0.4072	ambiguous	0.3939	ambiguous	0.149	Stabilizing	0.945	D	0.552	neutral	None	None	None	None	I
E/Q	0.1245	likely_benign	0.1122	benign	0.318	Stabilizing	0.864	D	0.527	neutral	N	0.50868867	None	None	I
E/R	0.2179	likely_benign	0.2018	benign	0.674	Stabilizing	0.945	D	0.588	neutral	None	None	None	None	I
E/S	0.1502	likely_benign	0.1367	benign	0.188	Stabilizing	0.547	D	0.553	neutral	None	None	None	None	I
E/T	0.1616	likely_benign	0.1442	benign	0.287	Stabilizing	0.894	D	0.493	neutral	None	None	None	None	I
E/V	0.1303	likely_benign	0.1164	benign	0.149	Stabilizing	0.928	D	0.568	neutral	N	0.478867195	None	None	I
E/W	0.8334	likely_pathogenic	0.8049	pathogenic	-0.069	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	I
E/Y	0.4995	ambiguous	0.4621	ambiguous	0.118	Stabilizing	0.995	D	0.577	neutral	None	None	None	None	I

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.