TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5042	15349;15350;15351	chr2:178734800;178734799;178734798	chr2:179599527;179599526;179599525
N2AB	4725	14398;14399;14400	chr2:178734800;178734799;178734798	chr2:179599527;179599526;179599525
N2A	3798	11617;11618;11619	chr2:178734800;178734799;178734798	chr2:179599527;179599526;179599525
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-33
• Domain position: 62
• Structural Position: 141
• Q(SASA): 0.4148
• 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
T/M	rs1060500462	None	0.004	N	0.213	0.087	0.210429274316	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
T/M	rs1060500462	None	0.004	N	0.213	0.087	0.210429274316	gnomAD-4.0.0	3.09861E-06	None	None	None	None	N	None	1.33518E-05	0	None	0	0	None	0	0	3.39047E-06	0	0
T/R	None	None	None	N	0.145	0.264	0.168933306366	gnomAD-4.0.0	6.84223E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99488E-07	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
T/A	0.0817	likely_benign	0.0744	benign	-0.696	Destabilizing	0.005	N	0.183	neutral	N	0.501563446	None	None	N
T/C	0.3822	ambiguous	0.35	ambiguous	-0.346	Destabilizing	0.628	D	0.377	neutral	None	None	None	None	N
T/D	0.3087	likely_benign	0.2668	benign	-0.205	Destabilizing	0.072	N	0.437	neutral	None	None	None	None	N
T/E	0.2477	likely_benign	0.2143	benign	-0.262	Destabilizing	0.031	N	0.386	neutral	None	None	None	None	N
T/F	0.203	likely_benign	0.1737	benign	-1.126	Destabilizing	0.038	N	0.509	neutral	None	None	None	None	N
T/G	0.2118	likely_benign	0.1853	benign	-0.861	Destabilizing	0.016	N	0.411	neutral	None	None	None	None	N
T/H	0.188	likely_benign	0.1687	benign	-1.279	Destabilizing	0.628	D	0.457	neutral	None	None	None	None	N
T/I	0.153	likely_benign	0.1289	benign	-0.366	Destabilizing	None	N	0.137	neutral	None	None	None	None	N
T/K	0.1481	likely_benign	0.1259	benign	-0.511	Destabilizing	0.001	N	0.109	neutral	N	0.494389913	None	None	N
T/L	0.0865	likely_benign	0.0777	benign	-0.366	Destabilizing	None	N	0.095	neutral	None	None	None	None	N
T/M	0.0824	likely_benign	0.0787	benign	0.116	Stabilizing	0.004	N	0.213	neutral	N	0.512068058	None	None	N
T/N	0.1066	likely_benign	0.0946	benign	-0.328	Destabilizing	0.072	N	0.266	neutral	None	None	None	None	N
T/P	0.1566	likely_benign	0.1261	benign	-0.447	Destabilizing	0.106	N	0.442	neutral	N	0.496047201	None	None	N
T/Q	0.1829	likely_benign	0.1595	benign	-0.65	Destabilizing	0.072	N	0.437	neutral	None	None	None	None	N
T/R	0.1118	likely_benign	0.101	benign	-0.213	Destabilizing	None	N	0.145	neutral	N	0.474812306	None	None	N
T/S	0.0934	likely_benign	0.0856	benign	-0.573	Destabilizing	None	N	0.082	neutral	N	0.448839391	None	None	N
T/V	0.128	likely_benign	0.1092	benign	-0.447	Destabilizing	0.007	N	0.18	neutral	None	None	None	None	N
T/W	0.4433	ambiguous	0.391	ambiguous	-1.043	Destabilizing	0.864	D	0.44	neutral	None	None	None	None	N
T/Y	0.2418	likely_benign	0.2092	benign	-0.785	Destabilizing	0.356	N	0.513	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.