TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20123	60592;60593;60594	chr2:178591358;178591357;178591356	chr2:179456085;179456084;179456083
N2AB	18482	55669;55670;55671	chr2:178591358;178591357;178591356	chr2:179456085;179456084;179456083
N2A	17555	52888;52889;52890	chr2:178591358;178591357;178591356	chr2:179456085;179456084;179456083
N2B	11058	33397;33398;33399	chr2:178591358;178591357;178591356	chr2:179456085;179456084;179456083
Novex-1	11183	33772;33773;33774	chr2:178591358;178591357;178591356	chr2:179456085;179456084;179456083
Novex-2	11250	33973;33974;33975	chr2:178591358;178591357;178591356	chr2:179456085;179456084;179456083
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-120
• Domain position: 44
• Structural Position: 102
• Q(SASA): 0.8351
• 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	rs1407608886	0.802	0.024	N	0.251	0.176	0.168933306366	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/K	rs1407608886	0.802	0.024	N	0.251	0.176	0.168933306366	gnomAD-4.0.0	1.36877E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99677E-07	1.15988E-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	0.0883	likely_benign	0.084	benign	-0.054	Destabilizing	0.012	N	0.299	neutral	N	0.471812645	None	None	N
E/C	0.5446	ambiguous	0.4871	ambiguous	-0.151	Destabilizing	0.864	D	0.201	neutral	None	None	None	None	N
E/D	0.0575	likely_benign	0.0526	benign	-0.244	Destabilizing	None	N	0.101	neutral	N	0.449415787	None	None	N
E/F	0.4807	ambiguous	0.4568	ambiguous	-0.137	Destabilizing	0.12	N	0.298	neutral	None	None	None	None	N
E/G	0.071	likely_benign	0.0675	benign	-0.158	Destabilizing	None	N	0.15	neutral	N	0.394485224	None	None	N
E/H	0.2326	likely_benign	0.2087	benign	0.444	Stabilizing	0.356	N	0.241	neutral	None	None	None	None	N
E/I	0.1932	likely_benign	0.1804	benign	0.158	Stabilizing	0.356	N	0.286	neutral	None	None	None	None	N
E/K	0.0885	likely_benign	0.0844	benign	0.377	Stabilizing	0.024	N	0.251	neutral	N	0.477295822	None	None	N
E/L	0.2154	likely_benign	0.2018	benign	0.158	Stabilizing	0.072	N	0.307	neutral	None	None	None	None	N
E/M	0.2702	likely_benign	0.2498	benign	-0.006	Destabilizing	0.628	D	0.223	neutral	None	None	None	None	N
E/N	0.0982	likely_benign	0.0854	benign	0.217	Stabilizing	0.038	N	0.232	neutral	None	None	None	None	N
E/P	0.2276	likely_benign	0.2306	benign	0.104	Stabilizing	0.136	N	0.31	neutral	None	None	None	None	N
E/Q	0.105	likely_benign	0.1018	benign	0.218	Stabilizing	0.055	N	0.265	neutral	N	0.498460528	None	None	N
E/R	0.1577	likely_benign	0.1483	benign	0.58	Stabilizing	0.072	N	0.245	neutral	None	None	None	None	N
E/S	0.0874	likely_benign	0.0783	benign	0.052	Stabilizing	0.016	N	0.282	neutral	None	None	None	None	N
E/T	0.11	likely_benign	0.1043	benign	0.143	Stabilizing	0.072	N	0.299	neutral	None	None	None	None	N
E/V	0.1375	likely_benign	0.1299	benign	0.104	Stabilizing	0.055	N	0.309	neutral	N	0.454339442	None	None	N
E/W	0.6849	likely_pathogenic	0.6488	pathogenic	-0.102	Destabilizing	0.864	D	0.2	neutral	None	None	None	None	N
E/Y	0.3452	ambiguous	0.3146	benign	0.08	Stabilizing	0.001	N	0.219	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.