TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22110	66553;66554;66555	chr2:178582041;178582040;178582039	chr2:179446768;179446767;179446766
N2AB	20469	61630;61631;61632	chr2:178582041;178582040;178582039	chr2:179446768;179446767;179446766
N2A	19542	58849;58850;58851	chr2:178582041;178582040;178582039	chr2:179446768;179446767;179446766
N2B	13045	39358;39359;39360	chr2:178582041;178582040;178582039	chr2:179446768;179446767;179446766
Novex-1	13170	39733;39734;39735	chr2:178582041;178582040;178582039	chr2:179446768;179446767;179446766
Novex-2	13237	39934;39935;39936	chr2:178582041;178582040;178582039	chr2:179446768;179446767;179446766
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: Fn3-48
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0878
• 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	None	None	0.012	N	0.513	0.202	0.50685403127	gnomAD-4.0.0	1.59213E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86038E-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
I/A	0.4019	ambiguous	0.4131	ambiguous	-2.026	Highly Destabilizing	0.007	N	0.439	neutral	None	None	None	None	N
I/C	0.6979	likely_pathogenic	0.691	pathogenic	-1.094	Destabilizing	0.356	N	0.561	neutral	None	None	None	None	N
I/D	0.9015	likely_pathogenic	0.8864	pathogenic	-1.898	Destabilizing	0.356	N	0.595	neutral	None	None	None	None	N
I/E	0.8303	likely_pathogenic	0.8173	pathogenic	-1.737	Destabilizing	0.136	N	0.59	neutral	None	None	None	None	N
I/F	0.37	ambiguous	0.35	ambiguous	-1.157	Destabilizing	0.055	N	0.572	neutral	N	0.518710875	None	None	N
I/G	0.6936	likely_pathogenic	0.6746	pathogenic	-2.502	Highly Destabilizing	0.136	N	0.555	neutral	None	None	None	None	N
I/H	0.8028	likely_pathogenic	0.7968	pathogenic	-1.866	Destabilizing	0.864	D	0.555	neutral	None	None	None	None	N
I/K	0.7824	likely_pathogenic	0.7648	pathogenic	-1.433	Destabilizing	0.136	N	0.588	neutral	None	None	None	None	N
I/L	0.1006	likely_benign	0.1074	benign	-0.697	Destabilizing	0.002	N	0.271	neutral	N	0.472746512	None	None	N
I/M	0.1321	likely_benign	0.1443	benign	-0.51	Destabilizing	0.171	N	0.575	neutral	N	0.478179186	None	None	N
I/N	0.4697	ambiguous	0.4657	ambiguous	-1.565	Destabilizing	0.56	D	0.571	neutral	N	0.5161105	None	None	N
I/P	0.9571	likely_pathogenic	0.9476	pathogenic	-1.115	Destabilizing	0.356	N	0.597	neutral	None	None	None	None	N
I/Q	0.6773	likely_pathogenic	0.6797	pathogenic	-1.524	Destabilizing	0.628	D	0.574	neutral	None	None	None	None	N
I/R	0.74	likely_pathogenic	0.7079	pathogenic	-1.066	Destabilizing	0.356	N	0.576	neutral	None	None	None	None	N
I/S	0.4458	ambiguous	0.4424	ambiguous	-2.25	Highly Destabilizing	0.055	N	0.535	neutral	N	0.46512432	None	None	N
I/T	0.3229	likely_benign	0.3516	ambiguous	-1.96	Destabilizing	0.012	N	0.513	neutral	N	0.448826716	None	None	N
I/V	0.0575	likely_benign	0.0565	benign	-1.115	Destabilizing	None	N	0.179	neutral	N	0.407425597	None	None	N
I/W	0.9525	likely_pathogenic	0.9517	pathogenic	-1.493	Destabilizing	0.864	D	0.579	neutral	None	None	None	None	N
I/Y	0.8075	likely_pathogenic	0.7846	pathogenic	-1.175	Destabilizing	0.356	N	0.603	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.