TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32716	98371;98372;98373	chr2:178539919;178539918;178539917	chr2:179404646;179404645;179404644
N2AB	31075	93448;93449;93450	chr2:178539919;178539918;178539917	chr2:179404646;179404645;179404644
N2A	30148	90667;90668;90669	chr2:178539919;178539918;178539917	chr2:179404646;179404645;179404644
N2B	23651	71176;71177;71178	chr2:178539919;178539918;178539917	chr2:179404646;179404645;179404644
Novex-1	23776	71551;71552;71553	chr2:178539919;178539918;178539917	chr2:179404646;179404645;179404644
Novex-2	23843	71752;71753;71754	chr2:178539919;178539918;178539917	chr2:179404646;179404645;179404644
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-155
• Domain position: 9
• Structural Position: 16
• Q(SASA): 0.1748
• 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
V/A	None	None	0.999	N	0.497	0.577	0.737036055105	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85838E-06	0	0
V/I	None	None	0.997	D	0.502	0.372	0.748681091053	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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
V/A	0.5851	likely_pathogenic	0.5064	ambiguous	-1.61	Destabilizing	0.999	D	0.497	neutral	N	0.520055748	None	None	N
V/C	0.8302	likely_pathogenic	0.8141	pathogenic	-1.169	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
V/D	0.9737	likely_pathogenic	0.9614	pathogenic	-1.531	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
V/E	0.9059	likely_pathogenic	0.8716	pathogenic	-1.448	Destabilizing	1.0	D	0.701	prob.neutral	D	0.52448323	None	None	N
V/F	0.5381	ambiguous	0.4943	ambiguous	-1.037	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
V/G	0.7392	likely_pathogenic	0.7001	pathogenic	-2.01	Highly Destabilizing	1.0	D	0.721	prob.delet.	D	0.535586046	None	None	N
V/H	0.9582	likely_pathogenic	0.9409	pathogenic	-1.605	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
V/I	0.112	likely_benign	0.1067	benign	-0.574	Destabilizing	0.997	D	0.502	neutral	D	0.536467996	None	None	N
V/K	0.9263	likely_pathogenic	0.8954	pathogenic	-1.399	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
V/L	0.4932	ambiguous	0.4657	ambiguous	-0.574	Destabilizing	0.997	D	0.517	neutral	N	0.489512034	None	None	N
V/M	0.519	ambiguous	0.46	ambiguous	-0.531	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
V/N	0.9393	likely_pathogenic	0.9144	pathogenic	-1.372	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/P	0.9746	likely_pathogenic	0.968	pathogenic	-0.886	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
V/Q	0.8494	likely_pathogenic	0.8077	pathogenic	-1.411	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/R	0.8791	likely_pathogenic	0.8385	pathogenic	-1.019	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/S	0.7754	likely_pathogenic	0.7093	pathogenic	-1.964	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/T	0.6518	likely_pathogenic	0.5686	pathogenic	-1.76	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
V/W	0.9803	likely_pathogenic	0.9742	pathogenic	-1.355	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
V/Y	0.9183	likely_pathogenic	0.894	pathogenic	-1.009	Destabilizing	1.0	D	0.733	prob.delet.	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.