TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30020	90283;90284;90285	chr2:178552842;178552841;178552840	chr2:179417569;179417568;179417567
N2AB	28379	85360;85361;85362	chr2:178552842;178552841;178552840	chr2:179417569;179417568;179417567
N2A	27452	82579;82580;82581	chr2:178552842;178552841;178552840	chr2:179417569;179417568;179417567
N2B	20955	63088;63089;63090	chr2:178552842;178552841;178552840	chr2:179417569;179417568;179417567
Novex-1	21080	63463;63464;63465	chr2:178552842;178552841;178552840	chr2:179417569;179417568;179417567
Novex-2	21147	63664;63665;63666	chr2:178552842;178552841;178552840	chr2:179417569;179417568;179417567
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: Fn3-106
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.2991
• 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/G	rs1320043628	-1.195	0.189	N	0.659	0.382	0.390842690916	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/G	rs1320043628	-1.195	0.189	N	0.659	0.382	0.390842690916	gnomAD-4.0.0	2.05263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31873E-05	1.6564E-05
E/K	rs1699956677	None	0.189	N	0.553	0.347	0.316198179892	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85812E-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	0.2936	likely_benign	0.3169	benign	-0.825	Destabilizing	0.189	N	0.591	neutral	N	0.476506892	None	None	N
E/C	0.886	likely_pathogenic	0.9046	pathogenic	-0.455	Destabilizing	0.962	D	0.725	deleterious	None	None	None	None	N
E/D	0.1796	likely_benign	0.2634	benign	-1.006	Destabilizing	None	N	0.247	neutral	N	0.470124109	None	None	N
E/F	0.8216	likely_pathogenic	0.8436	pathogenic	-0.017	Destabilizing	0.962	D	0.741	deleterious	None	None	None	None	N
E/G	0.4214	ambiguous	0.4527	ambiguous	-1.213	Destabilizing	0.189	N	0.659	prob.neutral	N	0.493547963	None	None	N
E/H	0.6601	likely_pathogenic	0.697	pathogenic	-0.185	Destabilizing	0.892	D	0.609	neutral	None	None	None	None	N
E/I	0.4387	ambiguous	0.4531	ambiguous	0.244	Stabilizing	0.687	D	0.741	deleterious	None	None	None	None	N
E/K	0.3367	likely_benign	0.3474	ambiguous	-0.526	Destabilizing	0.189	N	0.553	neutral	N	0.483014578	None	None	N
E/L	0.531	ambiguous	0.5663	pathogenic	0.244	Stabilizing	0.687	D	0.699	prob.delet.	None	None	None	None	N
E/M	0.5546	ambiguous	0.5584	ambiguous	0.621	Stabilizing	0.962	D	0.751	deleterious	None	None	None	None	N
E/N	0.4315	ambiguous	0.5222	ambiguous	-1.104	Destabilizing	0.351	N	0.595	neutral	None	None	None	None	N
E/P	0.8595	likely_pathogenic	0.91	pathogenic	-0.091	Destabilizing	0.687	D	0.609	neutral	None	None	None	None	N
E/Q	0.2219	likely_benign	0.2184	benign	-0.946	Destabilizing	0.449	N	0.6	neutral	N	0.466467259	None	None	N
E/R	0.5156	ambiguous	0.5475	ambiguous	-0.152	Destabilizing	0.519	D	0.586	neutral	None	None	None	None	N
E/S	0.3271	likely_benign	0.368	ambiguous	-1.43	Destabilizing	0.134	N	0.557	neutral	None	None	None	None	N
E/T	0.3504	ambiguous	0.3613	ambiguous	-1.101	Destabilizing	0.519	D	0.605	neutral	None	None	None	None	N
E/V	0.2708	likely_benign	0.288	benign	-0.091	Destabilizing	0.623	D	0.695	prob.delet.	N	0.483712595	None	None	N
E/W	0.9524	likely_pathogenic	0.9659	pathogenic	0.315	Stabilizing	0.962	D	0.73	deleterious	None	None	None	None	N
E/Y	0.7419	likely_pathogenic	0.7961	pathogenic	0.265	Stabilizing	0.962	D	0.745	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.