TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28369	85330;85331;85332	chr2:178561027;178561026;178561025	chr2:179425754;179425753;179425752
N2AB	26728	80407;80408;80409	chr2:178561027;178561026;178561025	chr2:179425754;179425753;179425752
N2A	25801	77626;77627;77628	chr2:178561027;178561026;178561025	chr2:179425754;179425753;179425752
N2B	19304	58135;58136;58137	chr2:178561027;178561026;178561025	chr2:179425754;179425753;179425752
Novex-1	19429	58510;58511;58512	chr2:178561027;178561026;178561025	chr2:179425754;179425753;179425752
Novex-2	19496	58711;58712;58713	chr2:178561027;178561026;178561025	chr2:179425754;179425753;179425752
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-143
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2832
• 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
V/A	None	None	0.052	D	0.404	0.321	0.620047664876	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/D	rs1703451641	None	0.484	D	0.543	0.644	0.848468935609	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/D	rs1703451641	None	0.484	D	0.543	0.644	0.848468935609	gnomAD-4.0.0	2.02995E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.4099E-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	0.4515	ambiguous	0.3846	ambiguous	-1.855	Destabilizing	0.052	N	0.404	neutral	D	0.528136514	None	None	I
V/C	0.8154	likely_pathogenic	0.7752	pathogenic	-1.246	Destabilizing	0.935	D	0.461	neutral	None	None	None	None	I
V/D	0.9121	likely_pathogenic	0.867	pathogenic	-2.086	Highly Destabilizing	0.484	N	0.543	neutral	D	0.556830626	None	None	I
V/E	0.7889	likely_pathogenic	0.7263	pathogenic	-2.038	Highly Destabilizing	0.555	D	0.467	neutral	None	None	None	None	I
V/F	0.3568	ambiguous	0.2943	benign	-1.337	Destabilizing	0.317	N	0.441	neutral	D	0.556070158	None	None	I
V/G	0.5669	likely_pathogenic	0.4752	ambiguous	-2.228	Highly Destabilizing	0.484	N	0.521	neutral	D	0.529825602	None	None	I
V/H	0.9013	likely_pathogenic	0.8577	pathogenic	-1.851	Destabilizing	0.935	D	0.554	neutral	None	None	None	None	I
V/I	0.0959	likely_benign	0.0835	benign	-0.893	Destabilizing	None	N	0.151	neutral	D	0.523000053	None	None	I
V/K	0.7251	likely_pathogenic	0.6615	pathogenic	-1.674	Destabilizing	0.555	D	0.466	neutral	None	None	None	None	I
V/L	0.2805	likely_benign	0.213	benign	-0.893	Destabilizing	0.009	N	0.369	neutral	N	0.512718397	None	None	I
V/M	0.2793	likely_benign	0.2263	benign	-0.667	Destabilizing	0.38	N	0.464	neutral	None	None	None	None	I
V/N	0.8272	likely_pathogenic	0.738	pathogenic	-1.544	Destabilizing	0.555	D	0.542	neutral	None	None	None	None	I
V/P	0.9543	likely_pathogenic	0.9299	pathogenic	-1.182	Destabilizing	0.791	D	0.485	neutral	None	None	None	None	I
V/Q	0.7103	likely_pathogenic	0.6417	pathogenic	-1.664	Destabilizing	0.791	D	0.505	neutral	None	None	None	None	I
V/R	0.6589	likely_pathogenic	0.5955	pathogenic	-1.156	Destabilizing	0.555	D	0.561	neutral	None	None	None	None	I
V/S	0.6685	likely_pathogenic	0.5725	pathogenic	-2.055	Highly Destabilizing	0.081	N	0.452	neutral	None	None	None	None	I
V/T	0.5018	ambiguous	0.4064	ambiguous	-1.902	Destabilizing	0.001	N	0.133	neutral	None	None	None	None	I
V/W	0.945	likely_pathogenic	0.915	pathogenic	-1.643	Destabilizing	0.935	D	0.611	neutral	None	None	None	None	I
V/Y	0.8052	likely_pathogenic	0.7341	pathogenic	-1.357	Destabilizing	0.555	D	0.463	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.