TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33669	101230;101231;101232	chr2:178535610;178535609;178535608	chr2:179400337;179400336;179400335
N2AB	32028	96307;96308;96309	chr2:178535610;178535609;178535608	chr2:179400337;179400336;179400335
N2A	31101	93526;93527;93528	chr2:178535610;178535609;178535608	chr2:179400337;179400336;179400335
N2B	24604	74035;74036;74037	chr2:178535610;178535609;178535608	chr2:179400337;179400336;179400335
Novex-1	24729	74410;74411;74412	chr2:178535610;178535609;178535608	chr2:179400337;179400336;179400335
Novex-2	24796	74611;74612;74613	chr2:178535610;178535609;178535608	chr2:179400337;179400336;179400335
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-159
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0932
• 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/I	rs1331642312	None	0.662	N	0.338	0.126	0.452640719197	gnomAD-4.0.0	3.42106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49732E-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	0.904	likely_pathogenic	0.8444	pathogenic	-2.0	Highly Destabilizing	0.999	D	0.697	prob.neutral	N	0.483280432	None	None	N
V/C	0.9693	likely_pathogenic	0.9626	pathogenic	-1.65	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/D	0.9994	likely_pathogenic	0.9988	pathogenic	-2.502	Highly Destabilizing	1.0	D	0.833	deleterious	N	0.45732841	None	None	N
V/E	0.9978	likely_pathogenic	0.9959	pathogenic	-2.317	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/F	0.9443	likely_pathogenic	0.8688	pathogenic	-1.197	Destabilizing	1.0	D	0.744	deleterious	N	0.455807473	None	None	N
V/G	0.9679	likely_pathogenic	0.9452	pathogenic	-2.522	Highly Destabilizing	1.0	D	0.83	deleterious	N	0.45707492	None	None	N
V/H	0.9994	likely_pathogenic	0.9988	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/I	0.1322	likely_benign	0.1083	benign	-0.561	Destabilizing	0.662	D	0.338	neutral	N	0.427925794	None	None	N
V/K	0.9986	likely_pathogenic	0.9974	pathogenic	-1.697	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
V/L	0.653	likely_pathogenic	0.5196	ambiguous	-0.561	Destabilizing	0.151	N	0.403	neutral	N	0.428387154	None	None	N
V/M	0.8639	likely_pathogenic	0.7418	pathogenic	-0.625	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
V/N	0.9976	likely_pathogenic	0.9951	pathogenic	-1.896	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/P	0.9958	likely_pathogenic	0.993	pathogenic	-1.011	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/Q	0.9976	likely_pathogenic	0.9954	pathogenic	-1.795	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/R	0.9967	likely_pathogenic	0.9944	pathogenic	-1.481	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/S	0.9874	likely_pathogenic	0.9764	pathogenic	-2.524	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/T	0.953	likely_pathogenic	0.9238	pathogenic	-2.195	Highly Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.999	pathogenic	-1.686	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/Y	0.9974	likely_pathogenic	0.9942	pathogenic	-1.315	Destabilizing	1.0	D	0.727	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.