TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27592	82999;83000;83001	chr2:178563358;178563357;178563356	chr2:179428085;179428084;179428083
N2AB	25951	78076;78077;78078	chr2:178563358;178563357;178563356	chr2:179428085;179428084;179428083
N2A	25024	75295;75296;75297	chr2:178563358;178563357;178563356	chr2:179428085;179428084;179428083
N2B	18527	55804;55805;55806	chr2:178563358;178563357;178563356	chr2:179428085;179428084;179428083
Novex-1	18652	56179;56180;56181	chr2:178563358;178563357;178563356	chr2:179428085;179428084;179428083
Novex-2	18719	56380;56381;56382	chr2:178563358;178563357;178563356	chr2:179428085;179428084;179428083
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-89
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.3983
• Predicted PPI site: I

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
S/N	None	None	None	N	0.121	0.076	0.0716867268079	gnomAD-4.0.0	1.5916E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85868E-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
S/A	0.1446	likely_benign	0.1301	benign	-0.539	Destabilizing	0.035	N	0.277	neutral	None	None	None	None	I
S/C	0.1175	likely_benign	0.1083	benign	-0.402	Destabilizing	0.915	D	0.485	neutral	N	0.478969789	None	None	I
S/D	0.4096	ambiguous	0.4067	ambiguous	-1.057	Destabilizing	0.081	N	0.389	neutral	None	None	None	None	I
S/E	0.5986	likely_pathogenic	0.5614	ambiguous	-0.937	Destabilizing	0.081	N	0.365	neutral	None	None	None	None	I
S/F	0.4699	ambiguous	0.3997	ambiguous	-0.485	Destabilizing	0.555	D	0.591	neutral	None	None	None	None	I
S/G	0.0681	likely_benign	0.0667	benign	-0.911	Destabilizing	None	N	0.12	neutral	N	0.481523498	None	None	I
S/H	0.2827	likely_benign	0.2569	benign	-1.535	Destabilizing	0.38	N	0.515	neutral	None	None	None	None	I
S/I	0.2137	likely_benign	0.1954	benign	0.371	Stabilizing	0.317	N	0.592	neutral	D	0.524890273	None	None	I
S/K	0.6891	likely_pathogenic	0.6474	pathogenic	-0.659	Destabilizing	0.081	N	0.364	neutral	None	None	None	None	I
S/L	0.2127	likely_benign	0.1816	benign	0.371	Stabilizing	0.081	N	0.519	neutral	None	None	None	None	I
S/M	0.2401	likely_benign	0.2204	benign	0.461	Stabilizing	0.935	D	0.491	neutral	None	None	None	None	I
S/N	0.0722	likely_benign	0.0699	benign	-1.091	Destabilizing	None	N	0.121	neutral	N	0.480752707	None	None	I
S/P	0.8297	likely_pathogenic	0.8218	pathogenic	0.106	Stabilizing	0.555	D	0.557	neutral	None	None	None	None	I
S/Q	0.4573	ambiguous	0.4203	ambiguous	-0.92	Destabilizing	0.38	N	0.474	neutral	None	None	None	None	I
S/R	0.6849	likely_pathogenic	0.6349	pathogenic	-0.923	Destabilizing	0.317	N	0.554	neutral	N	0.4819075	None	None	I
S/T	0.1088	likely_benign	0.1016	benign	-0.785	Destabilizing	None	N	0.152	neutral	N	0.431246606	None	None	I
S/V	0.2486	likely_benign	0.2342	benign	0.106	Stabilizing	0.081	N	0.562	neutral	None	None	None	None	I
S/W	0.5918	likely_pathogenic	0.52	ambiguous	-0.747	Destabilizing	0.935	D	0.619	neutral	None	None	None	None	I
S/Y	0.3074	likely_benign	0.2553	benign	-0.341	Destabilizing	0.791	D	0.589	neutral	None	None	None	None	I

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.