TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7129	21610;21611;21612	chr2:178723874;178723873;178723872	chr2:179588601;179588600;179588599
N2AB	6812	20659;20660;20661	chr2:178723874;178723873;178723872	chr2:179588601;179588600;179588599
N2A	5885	17878;17879;17880	chr2:178723874;178723873;178723872	chr2:179588601;179588600;179588599
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-55
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1162
• 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
A/T	None	None	0.989	N	0.613	0.432	0.432716982437	gnomAD-4.0.0	2.74159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70243E-06	1.16382E-05	0
A/V	rs2078875865	None	0.996	N	0.609	0.391	0.5578725173	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/V	rs2078875865	None	0.996	N	0.609	0.391	0.5578725173	gnomAD-4.0.0	2.48254E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39512E-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
A/C	0.8415	likely_pathogenic	0.8251	pathogenic	-1.269	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
A/D	0.8216	likely_pathogenic	0.7906	pathogenic	-1.491	Destabilizing	0.296	N	0.561	neutral	None	None	None	None	N
A/E	0.871	likely_pathogenic	0.8389	pathogenic	-1.485	Destabilizing	0.956	D	0.693	prob.neutral	D	0.56563881	None	None	N
A/F	0.8795	likely_pathogenic	0.8428	pathogenic	-1.125	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
A/G	0.1775	likely_benign	0.1653	benign	-1.334	Destabilizing	0.121	N	0.318	neutral	D	0.532024968	None	None	N
A/H	0.9589	likely_pathogenic	0.948	pathogenic	-1.481	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/I	0.7675	likely_pathogenic	0.7425	pathogenic	-0.38	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
A/K	0.9725	likely_pathogenic	0.9647	pathogenic	-1.202	Destabilizing	0.995	D	0.718	prob.delet.	None	None	None	None	N
A/L	0.6548	likely_pathogenic	0.6276	pathogenic	-0.38	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
A/M	0.6358	likely_pathogenic	0.6094	pathogenic	-0.44	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
A/N	0.828	likely_pathogenic	0.794	pathogenic	-1.069	Destabilizing	0.995	D	0.754	deleterious	None	None	None	None	N
A/P	0.9719	likely_pathogenic	0.9681	pathogenic	-0.559	Destabilizing	0.999	D	0.746	deleterious	D	0.554535994	None	None	N
A/Q	0.9153	likely_pathogenic	0.8972	pathogenic	-1.199	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
A/R	0.9442	likely_pathogenic	0.9306	pathogenic	-0.936	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
A/S	0.1776	likely_benign	0.1689	benign	-1.478	Destabilizing	0.978	D	0.514	neutral	N	0.4934356	None	None	N
A/T	0.2225	likely_benign	0.2065	benign	-1.369	Destabilizing	0.989	D	0.613	neutral	N	0.504703	None	None	N
A/V	0.4066	ambiguous	0.3866	ambiguous	-0.559	Destabilizing	0.996	D	0.609	neutral	N	0.484277659	None	None	N
A/W	0.9847	likely_pathogenic	0.9796	pathogenic	-1.489	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
A/Y	0.9396	likely_pathogenic	0.9181	pathogenic	-1.059	Destabilizing	1.0	D	0.755	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.