TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18095	54508;54509;54510	chr2:178604806;178604805;178604804	chr2:179469533;179469532;179469531
N2AB	16454	49585;49586;49587	chr2:178604806;178604805;178604804	chr2:179469533;179469532;179469531
N2A	15527	46804;46805;46806	chr2:178604806;178604805;178604804	chr2:179469533;179469532;179469531
N2B	9030	27313;27314;27315	chr2:178604806;178604805;178604804	chr2:179469533;179469532;179469531
Novex-1	9155	27688;27689;27690	chr2:178604806;178604805;178604804	chr2:179469533;179469532;179469531
Novex-2	9222	27889;27890;27891	chr2:178604806;178604805;178604804	chr2:179469533;179469532;179469531
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: Fn3-19
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2044
• 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/C	rs371747177	-0.545	0.995	N	0.629	0.347	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.66279E-04
S/G	None	None	0.008	N	0.364	0.117	0.107399877778	gnomAD-4.0.0	6.84708E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65837E-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
S/A	0.1443	likely_benign	0.1539	benign	-0.841	Destabilizing	0.415	N	0.604	neutral	None	None	None	None	I
S/C	0.1631	likely_benign	0.1784	benign	-0.53	Destabilizing	0.995	D	0.629	neutral	N	0.521561966	None	None	I
S/D	0.9093	likely_pathogenic	0.905	pathogenic	-0.274	Destabilizing	0.775	D	0.671	neutral	None	None	None	None	I
S/E	0.9512	likely_pathogenic	0.9503	pathogenic	-0.285	Destabilizing	0.875	D	0.671	neutral	None	None	None	None	I
S/F	0.8027	likely_pathogenic	0.8311	pathogenic	-1.087	Destabilizing	0.987	D	0.673	neutral	None	None	None	None	I
S/G	0.2634	likely_benign	0.274	benign	-1.078	Destabilizing	0.008	N	0.364	neutral	N	0.520708243	None	None	I
S/H	0.8752	likely_pathogenic	0.8861	pathogenic	-1.56	Destabilizing	0.996	D	0.617	neutral	None	None	None	None	I
S/I	0.7816	likely_pathogenic	0.7965	pathogenic	-0.318	Destabilizing	0.901	D	0.679	prob.neutral	N	0.50813718	None	None	I
S/K	0.9892	likely_pathogenic	0.9903	pathogenic	-0.748	Destabilizing	0.775	D	0.673	neutral	None	None	None	None	I
S/L	0.5011	ambiguous	0.5213	ambiguous	-0.318	Destabilizing	0.775	D	0.649	neutral	None	None	None	None	I
S/M	0.5417	ambiguous	0.5764	pathogenic	0.062	Stabilizing	0.996	D	0.617	neutral	None	None	None	None	I
S/N	0.5986	likely_pathogenic	0.6094	pathogenic	-0.679	Destabilizing	0.722	D	0.697	prob.neutral	N	0.485424569	None	None	I
S/P	0.9926	likely_pathogenic	0.9937	pathogenic	-0.46	Destabilizing	0.987	D	0.639	neutral	None	None	None	None	I
S/Q	0.9228	likely_pathogenic	0.928	pathogenic	-0.855	Destabilizing	0.987	D	0.658	neutral	None	None	None	None	I
S/R	0.9814	likely_pathogenic	0.983	pathogenic	-0.622	Destabilizing	0.949	D	0.631	neutral	N	0.517422796	None	None	I
S/T	0.2346	likely_benign	0.2483	benign	-0.721	Destabilizing	0.034	N	0.441	neutral	N	0.485774524	None	None	I
S/V	0.6528	likely_pathogenic	0.6728	pathogenic	-0.46	Destabilizing	0.923	D	0.661	neutral	None	None	None	None	I
S/W	0.8867	likely_pathogenic	0.8995	pathogenic	-1.034	Destabilizing	0.996	D	0.742	deleterious	None	None	None	None	I
S/Y	0.7837	likely_pathogenic	0.8032	pathogenic	-0.785	Destabilizing	0.987	D	0.669	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.