TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28080	84463;84464;84465	chr2:178561894;178561893;178561892	chr2:179426621;179426620;179426619
N2AB	26439	79540;79541;79542	chr2:178561894;178561893;178561892	chr2:179426621;179426620;179426619
N2A	25512	76759;76760;76761	chr2:178561894;178561893;178561892	chr2:179426621;179426620;179426619
N2B	19015	57268;57269;57270	chr2:178561894;178561893;178561892	chr2:179426621;179426620;179426619
Novex-1	19140	57643;57644;57645	chr2:178561894;178561893;178561892	chr2:179426621;179426620;179426619
Novex-2	19207	57844;57845;57846	chr2:178561894;178561893;178561892	chr2:179426621;179426620;179426619
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: Fn3-92
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.6414
• 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/A	None	None	0.002	N	0.165	0.176	0.229264304666	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/Q	rs1198142735	None	0.784	N	0.358	0.174	0.264081493735	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs1198142735	None	0.784	N	0.358	0.174	0.264081493735	gnomAD-4.0.0	2.5629E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78668E-06	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	0.0928	likely_benign	0.0876	benign	-0.086	Destabilizing	0.002	N	0.165	neutral	N	0.456566338	None	None	N
E/C	0.6548	likely_pathogenic	0.6118	pathogenic	-0.244	Destabilizing	0.995	D	0.294	neutral	None	None	None	None	N
E/D	0.109	likely_benign	0.0994	benign	-0.325	Destabilizing	0.006	N	0.17	neutral	N	0.487158604	None	None	N
E/F	0.5796	likely_pathogenic	0.5202	ambiguous	-0.045	Destabilizing	0.944	D	0.355	neutral	None	None	None	None	N
E/G	0.1434	likely_benign	0.1244	benign	-0.222	Destabilizing	0.473	N	0.357	neutral	N	0.51728951	None	None	N
E/H	0.3039	likely_benign	0.2776	benign	0.536	Stabilizing	0.981	D	0.342	neutral	None	None	None	None	N
E/I	0.1768	likely_benign	0.1549	benign	0.221	Stabilizing	0.031	N	0.231	neutral	None	None	None	None	N
E/K	0.0955	likely_benign	0.0894	benign	0.392	Stabilizing	0.642	D	0.32	neutral	N	0.434054838	None	None	N
E/L	0.211	likely_benign	0.1812	benign	0.221	Stabilizing	0.329	N	0.326	neutral	None	None	None	None	N
E/M	0.2824	likely_benign	0.2461	benign	-0.014	Destabilizing	0.944	D	0.325	neutral	None	None	None	None	N
E/N	0.1806	likely_benign	0.1568	benign	0.073	Stabilizing	0.543	D	0.359	neutral	None	None	None	None	N
E/P	0.3955	ambiguous	0.3541	ambiguous	0.137	Stabilizing	0.828	D	0.395	neutral	None	None	None	None	N
E/Q	0.1001	likely_benign	0.0957	benign	0.095	Stabilizing	0.784	D	0.358	neutral	N	0.475018813	None	None	N
E/R	0.1585	likely_benign	0.1496	benign	0.663	Stabilizing	0.828	D	0.346	neutral	None	None	None	None	N
E/S	0.1308	likely_benign	0.1174	benign	-0.056	Destabilizing	0.329	N	0.306	neutral	None	None	None	None	N
E/T	0.138	likely_benign	0.1241	benign	0.063	Stabilizing	0.013	N	0.151	neutral	None	None	None	None	N
E/V	0.1146	likely_benign	0.1059	benign	0.137	Stabilizing	0.27	N	0.304	neutral	N	0.515769357	None	None	N
E/W	0.7772	likely_pathogenic	0.738	pathogenic	0.036	Stabilizing	0.995	D	0.323	neutral	None	None	None	None	N
E/Y	0.4416	ambiguous	0.392	ambiguous	0.185	Stabilizing	0.981	D	0.357	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.