TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17991	54196;54197;54198	chr2:178605206;178605205;178605204	chr2:179469933;179469932;179469931
N2AB	16350	49273;49274;49275	chr2:178605206;178605205;178605204	chr2:179469933;179469932;179469931
N2A	15423	46492;46493;46494	chr2:178605206;178605205;178605204	chr2:179469933;179469932;179469931
N2B	8926	27001;27002;27003	chr2:178605206;178605205;178605204	chr2:179469933;179469932;179469931
Novex-1	9051	27376;27377;27378	chr2:178605206;178605205;178605204	chr2:179469933;179469932;179469931
Novex-2	9118	27577;27578;27579	chr2:178605206;178605205;178605204	chr2:179469933;179469932;179469931
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-114
• Domain position: 24
• Structural Position: 38
• Q(SASA): 0.6351
• 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
T/I	None	None	0.978	N	0.579	0.346	0.430239905395	gnomAD-4.0.0	2.73955E-06	None	None	None	None	I	None	0	0	None	0	2.5364E-05	None	0	0	9.00004E-07	2.32105E-05	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
T/A	0.107	likely_benign	0.1042	benign	-0.318	Destabilizing	0.994	D	0.379	neutral	N	0.486671107	None	None	I
T/C	0.4415	ambiguous	0.4575	ambiguous	-0.283	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
T/D	0.5805	likely_pathogenic	0.5754	pathogenic	0.032	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
T/E	0.4124	ambiguous	0.4286	ambiguous	-0.048	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
T/F	0.2823	likely_benign	0.2536	benign	-0.825	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	I
T/G	0.3223	likely_benign	0.3168	benign	-0.441	Destabilizing	1.0	D	0.592	neutral	None	None	None	None	I
T/H	0.3025	likely_benign	0.3001	benign	-0.714	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
T/I	0.1958	likely_benign	0.1794	benign	-0.118	Destabilizing	0.978	D	0.579	neutral	N	0.493117076	None	None	I
T/K	0.2789	likely_benign	0.2949	benign	-0.371	Destabilizing	0.999	D	0.619	neutral	N	0.454905405	None	None	I
T/L	0.1181	likely_benign	0.1105	benign	-0.118	Destabilizing	0.134	N	0.256	neutral	None	None	None	None	I
T/M	0.0992	likely_benign	0.0915	benign	0.032	Stabilizing	0.998	D	0.66	neutral	None	None	None	None	I
T/N	0.1852	likely_benign	0.164	benign	-0.153	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	I
T/P	0.7999	likely_pathogenic	0.7887	pathogenic	-0.156	Destabilizing	0.999	D	0.665	neutral	N	0.513422278	None	None	I
T/Q	0.2683	likely_benign	0.2797	benign	-0.402	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
T/R	0.2534	likely_benign	0.2653	benign	-0.064	Destabilizing	0.999	D	0.664	neutral	N	0.480379852	None	None	I
T/S	0.1294	likely_benign	0.1164	benign	-0.344	Destabilizing	0.998	D	0.398	neutral	N	0.455558766	None	None	I
T/V	0.1499	likely_benign	0.1413	benign	-0.156	Destabilizing	0.983	D	0.363	neutral	None	None	None	None	I
T/W	0.6551	likely_pathogenic	0.6466	pathogenic	-0.833	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
T/Y	0.3653	ambiguous	0.3521	ambiguous	-0.546	Destabilizing	1.0	D	0.674	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.