TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1331	4216;4217;4218	chr2:178779091;178779090;178779089	chr2:179643818;179643817;179643816
N2AB	1331	4216;4217;4218	chr2:178779091;178779090;178779089	chr2:179643818;179643817;179643816
N2A	1331	4216;4217;4218	chr2:178779091;178779090;178779089	chr2:179643818;179643817;179643816
N2B	1285	4078;4079;4080	chr2:178779091;178779090;178779089	chr2:179643818;179643817;179643816
Novex-1	1285	4078;4079;4080	chr2:178779091;178779090;178779089	chr2:179643818;179643817;179643816
Novex-2	1285	4078;4079;4080	chr2:178779091;178779090;178779089	chr2:179643818;179643817;179643816
Novex-3	1331	4216;4217;4218	chr2:178779091;178779090;178779089	chr2:179643818;179643817;179643816

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-5
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1519
• 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/T	rs2092527820	None	0.722	D	0.539	0.531	0.761228310999	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.9899	likely_pathogenic	0.9892	pathogenic	-2.352	Highly Destabilizing	0.415	N	0.502	neutral	None	None	None	None	N
I/C	0.9939	likely_pathogenic	0.9932	pathogenic	-1.407	Destabilizing	0.996	D	0.625	neutral	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9997	pathogenic	-2.94	Highly Destabilizing	0.987	D	0.735	prob.delet.	None	None	None	None	N
I/E	0.9979	likely_pathogenic	0.9974	pathogenic	-2.7	Highly Destabilizing	0.961	D	0.701	prob.neutral	None	None	None	None	N
I/F	0.9143	likely_pathogenic	0.8866	pathogenic	-1.55	Destabilizing	0.82	D	0.531	neutral	D	0.586467229	None	None	N
I/G	0.9981	likely_pathogenic	0.998	pathogenic	-2.844	Highly Destabilizing	0.961	D	0.684	prob.neutral	None	None	None	None	N
I/H	0.9987	likely_pathogenic	0.9982	pathogenic	-2.272	Highly Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
I/K	0.9953	likely_pathogenic	0.9942	pathogenic	-1.781	Destabilizing	0.961	D	0.692	prob.neutral	None	None	None	None	N
I/L	0.3507	ambiguous	0.3232	benign	-0.909	Destabilizing	0.003	N	0.165	neutral	N	0.49417038	None	None	N
I/M	0.5219	ambiguous	0.4658	ambiguous	-0.758	Destabilizing	0.901	D	0.571	neutral	D	0.589353165	None	None	N
I/N	0.9954	likely_pathogenic	0.994	pathogenic	-2.209	Highly Destabilizing	0.983	D	0.741	deleterious	D	0.699164501	None	None	N
I/P	0.9979	likely_pathogenic	0.9975	pathogenic	-1.376	Destabilizing	0.987	D	0.741	deleterious	None	None	None	None	N
I/Q	0.9961	likely_pathogenic	0.9951	pathogenic	-2.072	Highly Destabilizing	0.987	D	0.741	deleterious	None	None	None	None	N
I/R	0.9928	likely_pathogenic	0.9915	pathogenic	-1.59	Destabilizing	0.961	D	0.741	deleterious	None	None	None	None	N
I/S	0.9959	likely_pathogenic	0.9952	pathogenic	-2.783	Highly Destabilizing	0.901	D	0.611	neutral	D	0.636881975	None	None	N
I/T	0.9934	likely_pathogenic	0.9926	pathogenic	-2.402	Highly Destabilizing	0.722	D	0.539	neutral	D	0.715211934	None	None	N
I/V	0.3312	likely_benign	0.3494	ambiguous	-1.376	Destabilizing	0.003	N	0.158	neutral	N	0.506948187	None	None	N
I/W	0.9977	likely_pathogenic	0.9968	pathogenic	-1.915	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	N
I/Y	0.9927	likely_pathogenic	0.9905	pathogenic	-1.582	Destabilizing	0.961	D	0.659	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.