TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24377	73354;73355;73356	chr2:178573003;178573002;178573001	chr2:179437730;179437729;179437728
N2AB	22736	68431;68432;68433	chr2:178573003;178573002;178573001	chr2:179437730;179437729;179437728
N2A	21809	65650;65651;65652	chr2:178573003;178573002;178573001	chr2:179437730;179437729;179437728
N2B	15312	46159;46160;46161	chr2:178573003;178573002;178573001	chr2:179437730;179437729;179437728
Novex-1	15437	46534;46535;46536	chr2:178573003;178573002;178573001	chr2:179437730;179437729;179437728
Novex-2	15504	46735;46736;46737	chr2:178573003;178573002;178573001	chr2:179437730;179437729;179437728
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-65
• Domain position: 55
• Structural Position: 74
• Q(SASA): 0.7137
• 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
A/T	None	None	0.001	N	0.124	0.128	0.0611884634855	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-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
A/C	0.2651	likely_benign	0.2717	benign	-0.769	Destabilizing	0.676	D	0.265	neutral	None	None	None	None	I
A/D	0.1497	likely_benign	0.1518	benign	-0.496	Destabilizing	None	N	0.189	neutral	None	None	None	None	I
A/E	0.1372	likely_benign	0.143	benign	-0.651	Destabilizing	0.012	N	0.26	neutral	N	0.455411545	None	None	I
A/F	0.2056	likely_benign	0.2245	benign	-0.855	Destabilizing	0.356	N	0.373	neutral	None	None	None	None	I
A/G	0.099	likely_benign	0.1004	benign	-0.197	Destabilizing	0.012	N	0.189	neutral	N	0.46039329	None	None	I
A/H	0.2431	likely_benign	0.2527	benign	-0.209	Destabilizing	0.356	N	0.334	neutral	None	None	None	None	I
A/I	0.1327	likely_benign	0.1352	benign	-0.325	Destabilizing	0.038	N	0.358	neutral	None	None	None	None	I
A/K	0.2129	likely_benign	0.2123	benign	-0.551	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
A/L	0.1079	likely_benign	0.1098	benign	-0.325	Destabilizing	0.016	N	0.259	neutral	None	None	None	None	I
A/M	0.1319	likely_benign	0.1315	benign	-0.464	Destabilizing	0.356	N	0.274	neutral	None	None	None	None	I
A/N	0.1271	likely_benign	0.1295	benign	-0.228	Destabilizing	0.001	N	0.198	neutral	None	None	None	None	I
A/P	0.1396	likely_benign	0.1286	benign	-0.248	Destabilizing	0.055	N	0.367	neutral	N	0.475613459	None	None	I
A/Q	0.18	likely_benign	0.182	benign	-0.504	Destabilizing	0.214	N	0.354	neutral	None	None	None	None	I
A/R	0.2319	likely_benign	0.2272	benign	-0.099	Destabilizing	0.038	N	0.351	neutral	None	None	None	None	I
A/S	0.0763	likely_benign	0.0786	benign	-0.406	Destabilizing	None	N	0.141	neutral	N	0.495546014	None	None	I
A/T	0.0671	likely_benign	0.0674	benign	-0.487	Destabilizing	0.001	N	0.124	neutral	N	0.406601665	None	None	I
A/V	0.0844	likely_benign	0.083	benign	-0.248	Destabilizing	None	N	0.167	neutral	N	0.480040631	None	None	I
A/W	0.498	ambiguous	0.5071	ambiguous	-0.976	Destabilizing	0.864	D	0.413	neutral	None	None	None	None	I
A/Y	0.2593	likely_benign	0.2805	benign	-0.64	Destabilizing	0.356	N	0.362	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.