TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19725	59398;59399;59400	chr2:178592946;178592945;178592944	chr2:179457673;179457672;179457671
N2AB	18084	54475;54476;54477	chr2:178592946;178592945;178592944	chr2:179457673;179457672;179457671
N2A	17157	51694;51695;51696	chr2:178592946;178592945;178592944	chr2:179457673;179457672;179457671
N2B	10660	32203;32204;32205	chr2:178592946;178592945;178592944	chr2:179457673;179457672;179457671
Novex-1	10785	32578;32579;32580	chr2:178592946;178592945;178592944	chr2:179457673;179457672;179457671
Novex-2	10852	32779;32780;32781	chr2:178592946;178592945;178592944	chr2:179457673;179457672;179457671
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-31
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0476
• Predicted PPI site: N

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
E/K	rs767601396	0.739	0.698	N	0.604	0.263	0.339316883193	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	4.13E-05	0	None	0	5.14E-05	None	0	None	0	2.35E-05	0
E/K	rs767601396	0.739	0.698	N	0.604	0.263	0.339316883193	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs767601396	0.739	0.698	N	0.604	0.263	0.339316883193	gnomAD-4.0.0	1.61151E-05	None	None	None	None	N	None	0	0	None	0	2.23085E-05	None	0	0	1.94979E-05	1.09803E-05	1.60143E-05
E/Q	None	None	0.294	N	0.495	0.173	0.31291088546	gnomAD-4.0.0	6.84294E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65689E-05
E/V	rs1434751540	0.385	0.971	N	0.625	0.363	0.503186968135	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/V	rs1434751540	0.385	0.971	N	0.625	0.363	0.503186968135	gnomAD-4.0.0	3.18343E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85938E-06	1.43283E-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
E/A	0.1244	likely_benign	0.1222	benign	0.025	Stabilizing	0.822	D	0.593	neutral	N	0.501936056	None	None	N
E/C	0.7156	likely_pathogenic	0.7197	pathogenic	-0.106	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
E/D	0.086	likely_benign	0.0847	benign	-0.297	Destabilizing	0.014	N	0.44	neutral	N	0.423803346	None	None	N
E/F	0.6202	likely_pathogenic	0.6451	pathogenic	-0.101	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
E/G	0.1114	likely_benign	0.1105	benign	-0.07	Destabilizing	0.822	D	0.505	neutral	N	0.435150916	None	None	N
E/H	0.3592	ambiguous	0.3545	ambiguous	0.486	Stabilizing	0.994	D	0.645	neutral	None	None	None	None	N
E/I	0.2478	likely_benign	0.2475	benign	0.214	Stabilizing	0.978	D	0.68	prob.neutral	None	None	None	None	N
E/K	0.1033	likely_benign	0.0968	benign	0.437	Stabilizing	0.698	D	0.604	neutral	N	0.493777932	None	None	N
E/L	0.2773	likely_benign	0.2783	benign	0.214	Stabilizing	0.978	D	0.665	neutral	None	None	None	None	N
E/M	0.3129	likely_benign	0.321	benign	0.023	Stabilizing	0.998	D	0.633	neutral	None	None	None	None	N
E/N	0.1717	likely_benign	0.1604	benign	0.305	Stabilizing	0.915	D	0.597	neutral	None	None	None	None	N
E/P	0.3272	likely_benign	0.3485	ambiguous	0.169	Stabilizing	0.978	D	0.623	neutral	None	None	None	None	N
E/Q	0.1359	likely_benign	0.1333	benign	0.29	Stabilizing	0.294	N	0.495	neutral	N	0.498914393	None	None	N
E/R	0.1963	likely_benign	0.1927	benign	0.621	Stabilizing	0.956	D	0.639	neutral	None	None	None	None	N
E/S	0.1445	likely_benign	0.1406	benign	0.145	Stabilizing	0.86	D	0.607	neutral	None	None	None	None	N
E/T	0.1381	likely_benign	0.1314	benign	0.228	Stabilizing	0.956	D	0.589	neutral	None	None	None	None	N
E/V	0.1592	likely_benign	0.157	benign	0.169	Stabilizing	0.971	D	0.625	neutral	N	0.504533644	None	None	N
E/W	0.7814	likely_pathogenic	0.8038	pathogenic	-0.087	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/Y	0.49	ambiguous	0.5029	ambiguous	0.118	Stabilizing	0.993	D	0.635	neutral	None	None	None	None	N

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.