TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20350	61273;61274;61275	chr2:178590677;178590676;178590675	chr2:179455404;179455403;179455402
N2AB	18709	56350;56351;56352	chr2:178590677;178590676;178590675	chr2:179455404;179455403;179455402
N2A	17782	53569;53570;53571	chr2:178590677;178590676;178590675	chr2:179455404;179455403;179455402
N2B	11285	34078;34079;34080	chr2:178590677;178590676;178590675	chr2:179455404;179455403;179455402
Novex-1	11410	34453;34454;34455	chr2:178590677;178590676;178590675	chr2:179455404;179455403;179455402
Novex-2	11477	34654;34655;34656	chr2:178590677;178590676;178590675	chr2:179455404;179455403;179455402
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-35
• Domain position: 80
• Structural Position: 113
• Q(SASA): 1.0705
• 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
L/F	rs1162158537	-0.515	0.934	N	0.321	0.185	0.598957545849	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
L/F	rs1162158537	-0.515	0.934	N	0.321	0.185	0.598957545849	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	3.8835E-04	None	0	0	0	0	0
L/F	rs1162158537	-0.515	0.934	N	0.321	0.185	0.598957545849	gnomAD-4.0.0	8.07759E-05	None	None	None	None	I	None	0	0	None	0	1.45843E-03	None	0	0	4.79017E-06	0	2.8456E-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
L/A	0.1387	likely_benign	0.1678	benign	-0.346	Destabilizing	0.525	D	0.458	neutral	None	None	None	None	I
L/C	0.5226	ambiguous	0.6097	pathogenic	-0.61	Destabilizing	0.998	D	0.387	neutral	None	None	None	None	I
L/D	0.582	likely_pathogenic	0.6306	pathogenic	-0.051	Destabilizing	0.949	D	0.471	neutral	None	None	None	None	I
L/E	0.283	likely_benign	0.3148	benign	-0.158	Destabilizing	0.949	D	0.467	neutral	None	None	None	None	I
L/F	0.1569	likely_benign	0.1702	benign	-0.549	Destabilizing	0.934	D	0.321	neutral	N	0.514670492	None	None	I
L/G	0.4835	ambiguous	0.5391	ambiguous	-0.455	Destabilizing	0.728	D	0.521	neutral	None	None	None	None	I
L/H	0.2061	likely_benign	0.2347	benign	0.107	Stabilizing	0.997	D	0.427	neutral	N	0.476978896	None	None	I
L/I	0.0813	likely_benign	0.0807	benign	-0.194	Destabilizing	0.005	N	0.113	neutral	N	0.369851431	None	None	I
L/K	0.208	likely_benign	0.2233	benign	-0.135	Destabilizing	0.842	D	0.477	neutral	None	None	None	None	I
L/M	0.0948	likely_benign	0.1047	benign	-0.316	Destabilizing	0.172	N	0.251	neutral	None	None	None	None	I
L/N	0.3385	likely_benign	0.367	ambiguous	0.035	Stabilizing	0.949	D	0.48	neutral	None	None	None	None	I
L/P	0.3639	ambiguous	0.394	ambiguous	-0.214	Destabilizing	0.966	D	0.472	neutral	N	0.447696139	None	None	I
L/Q	0.1315	likely_benign	0.146	benign	-0.18	Destabilizing	0.974	D	0.475	neutral	None	None	None	None	I
L/R	0.168	likely_benign	0.1984	benign	0.342	Stabilizing	0.934	D	0.479	neutral	N	0.403827932	None	None	I
L/S	0.2039	likely_benign	0.2333	benign	-0.37	Destabilizing	0.067	N	0.384	neutral	None	None	None	None	I
L/T	0.1567	likely_benign	0.1767	benign	-0.372	Destabilizing	0.728	D	0.459	neutral	None	None	None	None	I
L/V	0.0854	likely_benign	0.0908	benign	-0.214	Destabilizing	0.267	N	0.273	neutral	N	0.423125768	None	None	I
L/W	0.2753	likely_benign	0.3046	benign	-0.578	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	I
L/Y	0.3263	likely_benign	0.3582	ambiguous	-0.303	Destabilizing	0.974	D	0.406	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.