TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28278	85057;85058;85059	chr2:178561300;178561299;178561298	chr2:179426027;179426026;179426025
N2AB	26637	80134;80135;80136	chr2:178561300;178561299;178561298	chr2:179426027;179426026;179426025
N2A	25710	77353;77354;77355	chr2:178561300;178561299;178561298	chr2:179426027;179426026;179426025
N2B	19213	57862;57863;57864	chr2:178561300;178561299;178561298	chr2:179426027;179426026;179426025
Novex-1	19338	58237;58238;58239	chr2:178561300;178561299;178561298	chr2:179426027;179426026;179426025
Novex-2	19405	58438;58439;58440	chr2:178561300;178561299;178561298	chr2:179426027;179426026;179426025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-94
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.866
• 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
Y/D	rs1336515508	1.122	0.942	N	0.649	0.359	0.472344434578	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
Y/D	rs1336515508	1.122	0.942	N	0.649	0.359	0.472344434578	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
Y/D	rs1336515508	1.122	0.942	N	0.649	0.359	0.472344434578	gnomAD-4.0.0	2.56221E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.7857E-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
Y/A	0.7124	likely_pathogenic	0.6994	pathogenic	-0.71	Destabilizing	0.86	D	0.519	neutral	None	None	None	None	I
Y/C	0.2615	likely_benign	0.2514	benign	0.295	Stabilizing	0.997	D	0.666	neutral	N	0.486796332	None	None	I
Y/D	0.4271	ambiguous	0.4312	ambiguous	0.879	Stabilizing	0.942	D	0.649	neutral	N	0.478088043	None	None	I
Y/E	0.8162	likely_pathogenic	0.7961	pathogenic	0.845	Stabilizing	0.956	D	0.531	neutral	None	None	None	None	I
Y/F	0.1165	likely_benign	0.1156	benign	-0.492	Destabilizing	0.014	N	0.311	neutral	N	0.480496417	None	None	I
Y/G	0.5016	ambiguous	0.5065	ambiguous	-0.895	Destabilizing	0.956	D	0.555	neutral	None	None	None	None	I
Y/H	0.2445	likely_benign	0.2246	benign	0.136	Stabilizing	0.032	N	0.286	neutral	N	0.504103995	None	None	I
Y/I	0.7649	likely_pathogenic	0.758	pathogenic	-0.254	Destabilizing	0.956	D	0.486	neutral	None	None	None	None	I
Y/K	0.7708	likely_pathogenic	0.739	pathogenic	0.361	Stabilizing	0.956	D	0.611	neutral	None	None	None	None	I
Y/L	0.6726	likely_pathogenic	0.672	pathogenic	-0.254	Destabilizing	0.754	D	0.537	neutral	None	None	None	None	I
Y/M	0.7819	likely_pathogenic	0.7845	pathogenic	0.076	Stabilizing	0.998	D	0.522	neutral	None	None	None	None	I
Y/N	0.1903	likely_benign	0.2214	benign	0.29	Stabilizing	0.942	D	0.618	neutral	N	0.467239118	None	None	I
Y/P	0.9758	likely_pathogenic	0.9733	pathogenic	-0.385	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	I
Y/Q	0.6775	likely_pathogenic	0.6462	pathogenic	0.248	Stabilizing	0.956	D	0.52	neutral	None	None	None	None	I
Y/R	0.5441	ambiguous	0.4941	ambiguous	0.69	Stabilizing	0.956	D	0.619	neutral	None	None	None	None	I
Y/S	0.2958	likely_benign	0.289	benign	-0.173	Destabilizing	0.942	D	0.509	neutral	N	0.493905644	None	None	I
Y/T	0.6046	likely_pathogenic	0.5907	pathogenic	-0.115	Destabilizing	0.978	D	0.608	neutral	None	None	None	None	I
Y/V	0.6599	likely_pathogenic	0.6395	pathogenic	-0.385	Destabilizing	0.86	D	0.506	neutral	None	None	None	None	I
Y/W	0.5389	ambiguous	0.5167	ambiguous	-0.614	Destabilizing	0.998	D	0.5	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.