TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14365	43318;43319;43320	chr2:178633038;178633037;178633036	chr2:179497765;179497764;179497763
N2AB	12724	38395;38396;38397	chr2:178633038;178633037;178633036	chr2:179497765;179497764;179497763
N2A	11797	35614;35615;35616	chr2:178633038;178633037;178633036	chr2:179497765;179497764;179497763
N2B	5300	16123;16124;16125	chr2:178633038;178633037;178633036	chr2:179497765;179497764;179497763
Novex-1	5425	16498;16499;16500	chr2:178633038;178633037;178633036	chr2:179497765;179497764;179497763
Novex-2	5492	16699;16700;16701	chr2:178633038;178633037;178633036	chr2:179497765;179497764;179497763
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: Ig-94
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.1275
• 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	rs1302907540	None	0.997	N	0.757	0.416	0.276898752692	gnomAD-4.0.0	9.60257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.05E-05	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
E/A	0.3928	ambiguous	0.4104	ambiguous	-0.8	Destabilizing	0.997	D	0.768	deleterious	N	0.518723598	None	None	N
E/C	0.9593	likely_pathogenic	0.9675	pathogenic	-0.46	Destabilizing	1.0	D	0.652	prob.neutral	None	None	None	None	N
E/D	0.3155	likely_benign	0.301	benign	-1.256	Destabilizing	0.997	D	0.683	prob.neutral	N	0.419482867	None	None	N
E/F	0.9332	likely_pathogenic	0.9376	pathogenic	-0.22	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/G	0.481	ambiguous	0.5063	ambiguous	-1.2	Destabilizing	0.999	D	0.665	prob.neutral	N	0.520589675	None	None	N
E/H	0.6716	likely_pathogenic	0.6677	pathogenic	-0.599	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
E/I	0.6137	likely_pathogenic	0.6342	pathogenic	0.3	Stabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
E/K	0.1856	likely_benign	0.193	benign	-0.75	Destabilizing	0.997	D	0.757	deleterious	N	0.432052863	None	None	N
E/L	0.7217	likely_pathogenic	0.742	pathogenic	0.3	Stabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
E/M	0.6939	likely_pathogenic	0.7123	pathogenic	0.789	Stabilizing	1.0	D	0.663	prob.neutral	None	None	None	None	N
E/N	0.52	ambiguous	0.5056	ambiguous	-1.239	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
E/P	0.9775	likely_pathogenic	0.9846	pathogenic	-0.045	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/Q	0.1929	likely_benign	0.1917	benign	-1.054	Destabilizing	0.999	D	0.72	deleterious	N	0.433474754	None	None	N
E/R	0.3581	ambiguous	0.3655	ambiguous	-0.506	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
E/S	0.4377	ambiguous	0.4206	ambiguous	-1.581	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
E/T	0.4258	ambiguous	0.4124	ambiguous	-1.245	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
E/V	0.4209	ambiguous	0.4421	ambiguous	-0.045	Destabilizing	0.999	D	0.665	prob.neutral	N	0.477503867	None	None	N
E/W	0.9754	likely_pathogenic	0.977	pathogenic	-0.018	Destabilizing	1.0	D	0.65	prob.neutral	None	None	None	None	N
E/Y	0.8724	likely_pathogenic	0.877	pathogenic	0.016	Stabilizing	1.0	D	0.647	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.