TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24963	75112;75113;75114	chr2:178571245;178571244;178571243	chr2:179435972;179435971;179435970
N2AB	23322	70189;70190;70191	chr2:178571245;178571244;178571243	chr2:179435972;179435971;179435970
N2A	22395	67408;67409;67410	chr2:178571245;178571244;178571243	chr2:179435972;179435971;179435970
N2B	15898	47917;47918;47919	chr2:178571245;178571244;178571243	chr2:179435972;179435971;179435970
Novex-1	16023	48292;48293;48294	chr2:178571245;178571244;178571243	chr2:179435972;179435971;179435970
Novex-2	16090	48493;48494;48495	chr2:178571245;178571244;178571243	chr2:179435972;179435971;179435970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-69
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0789
• 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
I/V	rs769512290	-1.19	0.58	N	0.427	0.047	0.367803931526	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.15949E-04	None	0	0	None	0	None	0	0	0
I/V	rs769512290	-1.19	0.58	N	0.427	0.047	0.367803931526	gnomAD-4.0.0	7.95912E-06	None	None	None	None	N	None	0	1.14354E-04	None	0	0	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
I/A	0.8482	likely_pathogenic	0.8597	pathogenic	-2.345	Highly Destabilizing	0.953	D	0.537	neutral	None	None	None	None	N
I/C	0.8484	likely_pathogenic	0.862	pathogenic	-1.387	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
I/D	0.9883	likely_pathogenic	0.9889	pathogenic	-2.832	Highly Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
I/E	0.975	likely_pathogenic	0.9757	pathogenic	-2.574	Highly Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
I/F	0.5998	likely_pathogenic	0.6294	pathogenic	-1.379	Destabilizing	0.982	D	0.674	neutral	N	0.492991759	None	None	N
I/G	0.9714	likely_pathogenic	0.9758	pathogenic	-2.905	Highly Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
I/H	0.9561	likely_pathogenic	0.9572	pathogenic	-2.54	Highly Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
I/K	0.9568	likely_pathogenic	0.9568	pathogenic	-1.65	Destabilizing	0.993	D	0.787	deleterious	None	None	None	None	N
I/L	0.1612	likely_benign	0.1787	benign	-0.707	Destabilizing	0.02	N	0.255	neutral	N	0.51211019	None	None	N
I/M	0.2712	likely_benign	0.2813	benign	-0.617	Destabilizing	0.982	D	0.677	prob.neutral	N	0.499739708	None	None	N
I/N	0.8487	likely_pathogenic	0.8517	pathogenic	-2.081	Highly Destabilizing	0.997	D	0.8	deleterious	N	0.487734612	None	None	N
I/P	0.9787	likely_pathogenic	0.98	pathogenic	-1.238	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
I/Q	0.9435	likely_pathogenic	0.9439	pathogenic	-1.878	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
I/R	0.9403	likely_pathogenic	0.94	pathogenic	-1.538	Destabilizing	0.993	D	0.8	deleterious	None	None	None	None	N
I/S	0.8453	likely_pathogenic	0.8442	pathogenic	-2.711	Highly Destabilizing	0.991	D	0.697	prob.neutral	N	0.505317503	None	None	N
I/T	0.8669	likely_pathogenic	0.8701	pathogenic	-2.308	Highly Destabilizing	0.991	D	0.689	prob.neutral	N	0.46754367	None	None	N
I/V	0.1111	likely_benign	0.1109	benign	-1.238	Destabilizing	0.58	D	0.427	neutral	N	0.469340848	None	None	N
I/W	0.981	likely_pathogenic	0.9839	pathogenic	-1.871	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
I/Y	0.9258	likely_pathogenic	0.9378	pathogenic	-1.532	Destabilizing	0.993	D	0.698	prob.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.