TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16960	51103;51104;51105	chr2:178611251;178611250;178611249	chr2:179475978;179475977;179475976
N2AB	15319	46180;46181;46182	chr2:178611251;178611250;178611249	chr2:179475978;179475977;179475976
N2A	14392	43399;43400;43401	chr2:178611251;178611250;178611249	chr2:179475978;179475977;179475976
N2B	7895	23908;23909;23910	chr2:178611251;178611250;178611249	chr2:179475978;179475977;179475976
Novex-1	8020	24283;24284;24285	chr2:178611251;178611250;178611249	chr2:179475978;179475977;179475976
Novex-2	8087	24484;24485;24486	chr2:178611251;178611250;178611249	chr2:179475978;179475977;179475976
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-111
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7875
• 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
E/K	None	None	0.005	N	0.137	0.185	0.238705975628	gnomAD-4.0.0	6.84804E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99888E-07	0	0
E/Q	rs1210274436	0.075	0.022	N	0.129	0.09	0.279370189704	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/Q	rs1210274436	0.075	0.022	N	0.129	0.09	0.279370189704	gnomAD-4.0.0	6.84804E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.1609E-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	0.1372	likely_benign	0.1366	benign	0.041	Stabilizing	0.625	D	0.422	neutral	N	0.484932479	None	None	I
E/C	0.7809	likely_pathogenic	0.7781	pathogenic	-0.228	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	I
E/D	0.1218	likely_benign	0.1206	benign	-0.288	Destabilizing	0.625	D	0.412	neutral	N	0.481438678	None	None	I
E/F	0.7314	likely_pathogenic	0.7281	pathogenic	-0.049	Destabilizing	0.991	D	0.457	neutral	None	None	None	None	I
E/G	0.1352	likely_benign	0.1354	benign	-0.055	Destabilizing	0.801	D	0.459	neutral	N	0.497586807	None	None	I
E/H	0.3773	ambiguous	0.3709	ambiguous	0.6	Stabilizing	0.974	D	0.451	neutral	None	None	None	None	I
E/I	0.3725	ambiguous	0.3617	ambiguous	0.233	Stabilizing	0.974	D	0.467	neutral	None	None	None	None	I
E/K	0.1202	likely_benign	0.1148	benign	0.37	Stabilizing	0.005	N	0.137	neutral	N	0.49906526	None	None	I
E/L	0.3443	ambiguous	0.3384	benign	0.233	Stabilizing	0.842	D	0.47	neutral	None	None	None	None	I
E/M	0.4269	ambiguous	0.4163	ambiguous	-0.037	Destabilizing	0.991	D	0.451	neutral	None	None	None	None	I
E/N	0.209	likely_benign	0.2147	benign	0.21	Stabilizing	0.842	D	0.432	neutral	None	None	None	None	I
E/P	0.3266	likely_benign	0.3151	benign	0.186	Stabilizing	0.974	D	0.448	neutral	None	None	None	None	I
E/Q	0.1141	likely_benign	0.1111	benign	0.205	Stabilizing	0.022	N	0.129	neutral	N	0.467646623	None	None	I
E/R	0.2169	likely_benign	0.2112	benign	0.6	Stabilizing	0.728	D	0.402	neutral	None	None	None	None	I
E/S	0.1736	likely_benign	0.1845	benign	0.047	Stabilizing	0.842	D	0.399	neutral	None	None	None	None	I
E/T	0.2004	likely_benign	0.1978	benign	0.133	Stabilizing	0.842	D	0.463	neutral	None	None	None	None	I
E/V	0.216	likely_benign	0.207	benign	0.186	Stabilizing	0.891	D	0.447	neutral	N	0.505918342	None	None	I
E/W	0.8684	likely_pathogenic	0.8588	pathogenic	-0.031	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	I
E/Y	0.6064	likely_pathogenic	0.585	pathogenic	0.168	Stabilizing	0.991	D	0.469	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.