TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4853	14782;14783;14784	chr2:178735889;178735888;178735887	chr2:179600616;179600615;179600614
N2AB	4536	13831;13832;13833	chr2:178735889;178735888;178735887	chr2:179600616;179600615;179600614
N2A	3609	11050;11051;11052	chr2:178735889;178735888;178735887	chr2:179600616;179600615;179600614
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-31
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2169
• 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	rs1264041107	-1.189	0.4	N	0.469	0.212	0.323886383625	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/A	rs1264041107	-1.189	0.4	N	0.469	0.212	0.323886383625	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46998E-05	0	0
E/Q	None	None	0.997	N	0.585	0.27	0.356690202451	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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	0.2684	likely_benign	0.1964	benign	-0.859	Destabilizing	0.4	N	0.469	neutral	N	0.510854535	None	None	N
E/C	0.8839	likely_pathogenic	0.8285	pathogenic	-0.507	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/D	0.3795	ambiguous	0.2731	benign	-1.348	Destabilizing	0.99	D	0.584	neutral	N	0.511392063	None	None	N
E/F	0.7582	likely_pathogenic	0.6707	pathogenic	-0.325	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
E/G	0.3953	ambiguous	0.2899	benign	-1.267	Destabilizing	0.98	D	0.561	neutral	D	0.618775221	None	None	N
E/H	0.5005	ambiguous	0.397	ambiguous	-0.695	Destabilizing	0.323	N	0.475	neutral	None	None	None	None	N
E/I	0.4221	ambiguous	0.3227	benign	0.268	Stabilizing	0.991	D	0.653	neutral	None	None	None	None	N
E/K	0.3448	ambiguous	0.2549	benign	-0.755	Destabilizing	0.99	D	0.578	neutral	N	0.495912429	None	None	N
E/L	0.482	ambiguous	0.3612	ambiguous	0.268	Stabilizing	0.171	N	0.574	neutral	None	None	None	None	N
E/M	0.5452	ambiguous	0.4365	ambiguous	0.774	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/N	0.5537	ambiguous	0.3994	ambiguous	-1.229	Destabilizing	0.996	D	0.573	neutral	None	None	None	None	N
E/P	0.9792	likely_pathogenic	0.9628	pathogenic	-0.086	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
E/Q	0.1564	likely_benign	0.121	benign	-1.051	Destabilizing	0.997	D	0.585	neutral	N	0.504414832	None	None	N
E/R	0.4625	ambiguous	0.3548	ambiguous	-0.562	Destabilizing	0.996	D	0.575	neutral	None	None	None	None	N
E/S	0.3576	ambiguous	0.2619	benign	-1.63	Destabilizing	0.971	D	0.567	neutral	None	None	None	None	N
E/T	0.3449	ambiguous	0.2535	benign	-1.28	Destabilizing	0.985	D	0.537	neutral	None	None	None	None	N
E/V	0.2586	likely_benign	0.1967	benign	-0.086	Destabilizing	0.961	D	0.561	neutral	N	0.457223387	None	None	N
E/W	0.9096	likely_pathogenic	0.8596	pathogenic	-0.143	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/Y	0.6576	likely_pathogenic	0.5465	ambiguous	-0.07	Destabilizing	0.996	D	0.643	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.