TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18841	56746;56747;56748	chr2:178599272;178599271;178599270	chr2:179463999;179463998;179463997
N2AB	17200	51823;51824;51825	chr2:178599272;178599271;178599270	chr2:179463999;179463998;179463997
N2A	16273	49042;49043;49044	chr2:178599272;178599271;178599270	chr2:179463999;179463998;179463997
N2B	9776	29551;29552;29553	chr2:178599272;178599271;178599270	chr2:179463999;179463998;179463997
Novex-1	9901	29926;29927;29928	chr2:178599272;178599271;178599270	chr2:179463999;179463998;179463997
Novex-2	9968	30127;30128;30129	chr2:178599272;178599271;178599270	chr2:179463999;179463998;179463997
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: Fn3-24
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.4055
• 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	rs376621189	0.242	0.998	N	0.558	0.378	None	gnomAD-2.1.1	4.3E-06	None	None	None	None	N	None	6.57E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs376621189	0.242	0.998	N	0.558	0.378	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs376621189	0.242	0.998	N	0.558	0.378	None	gnomAD-4.0.0	2.50656E-06	None	None	None	None	N	None	5.41052E-05	0	None	0	0	None	0	0	0	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	0.1182	likely_benign	0.1078	benign	-0.266	Destabilizing	0.998	D	0.659	neutral	N	0.493335215	None	None	N
E/C	0.7629	likely_pathogenic	0.7002	pathogenic	-0.333	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/D	0.0944	likely_benign	0.0951	benign	-0.411	Destabilizing	0.434	N	0.189	neutral	N	0.447296281	None	None	N
E/F	0.6368	likely_pathogenic	0.5672	pathogenic	-0.027	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/G	0.135	likely_benign	0.1211	benign	-0.462	Destabilizing	0.999	D	0.687	prob.neutral	N	0.482929007	None	None	N
E/H	0.431	ambiguous	0.357	ambiguous	0.466	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/I	0.2573	likely_benign	0.2216	benign	0.217	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
E/K	0.1898	likely_benign	0.1457	benign	0.225	Stabilizing	0.998	D	0.558	neutral	N	0.455875692	None	None	N
E/L	0.3336	likely_benign	0.299	benign	0.217	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/M	0.3859	ambiguous	0.3347	benign	0.04	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/N	0.1886	likely_benign	0.168	benign	-0.21	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
E/P	0.7226	likely_pathogenic	0.5975	pathogenic	0.076	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/Q	0.1499	likely_benign	0.1305	benign	-0.151	Destabilizing	0.999	D	0.637	neutral	N	0.488276112	None	None	N
E/R	0.3131	likely_benign	0.2388	benign	0.593	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/S	0.1751	likely_benign	0.1534	benign	-0.353	Destabilizing	0.997	D	0.603	neutral	None	None	None	None	N
E/T	0.1584	likely_benign	0.1406	benign	-0.185	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/V	0.1493	likely_benign	0.1334	benign	0.076	Stabilizing	1.0	D	0.725	prob.delet.	N	0.493818005	None	None	N
E/W	0.8706	likely_pathogenic	0.8128	pathogenic	0.132	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/Y	0.4864	ambiguous	0.4142	ambiguous	0.218	Stabilizing	1.0	D	0.732	prob.delet.	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.