TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30023	90292;90293;90294	chr2:178552833;178552832;178552831	chr2:179417560;179417559;179417558
N2AB	28382	85369;85370;85371	chr2:178552833;178552832;178552831	chr2:179417560;179417559;179417558
N2A	27455	82588;82589;82590	chr2:178552833;178552832;178552831	chr2:179417560;179417559;179417558
N2B	20958	63097;63098;63099	chr2:178552833;178552832;178552831	chr2:179417560;179417559;179417558
Novex-1	21083	63472;63473;63474	chr2:178552833;178552832;178552831	chr2:179417560;179417559;179417558
Novex-2	21150	63673;63674;63675	chr2:178552833;178552832;178552831	chr2:179417560;179417559;179417558
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: Fn3-106
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.6398
• 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	None	None	0.191	N	0.499	0.205	0.263140351381	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	5.65227E-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	0.1491	likely_benign	0.1516	benign	-0.162	Destabilizing	0.191	N	0.483	neutral	N	0.465729563	None	None	N
E/C	0.8342	likely_pathogenic	0.8518	pathogenic	-0.344	Destabilizing	0.981	D	0.819	deleterious	None	None	None	None	N
E/D	0.1002	likely_benign	0.1018	benign	-0.321	Destabilizing	0.001	N	0.18	neutral	N	0.442730249	None	None	N
E/F	0.6946	likely_pathogenic	0.7159	pathogenic	None	Stabilizing	0.931	D	0.77	deleterious	None	None	None	None	N
E/G	0.1859	likely_benign	0.1874	benign	-0.319	Destabilizing	0.001	N	0.446	neutral	N	0.504413426	None	None	N
E/H	0.4872	ambiguous	0.5034	ambiguous	0.625	Stabilizing	0.817	D	0.485	neutral	None	None	None	None	N
E/I	0.2817	likely_benign	0.2945	benign	0.208	Stabilizing	0.817	D	0.791	deleterious	None	None	None	None	N
E/K	0.1851	likely_benign	0.1915	benign	0.342	Stabilizing	0.191	N	0.499	neutral	N	0.463781007	None	None	N
E/L	0.3502	ambiguous	0.3593	ambiguous	0.208	Stabilizing	0.687	D	0.628	neutral	None	None	None	None	N
E/M	0.392	ambiguous	0.409	ambiguous	-0.049	Destabilizing	0.944	D	0.747	deleterious	None	None	None	None	N
E/N	0.2242	likely_benign	0.237	benign	-0.093	Destabilizing	0.239	N	0.533	neutral	None	None	None	None	N
E/P	0.8338	likely_pathogenic	0.8253	pathogenic	0.103	Stabilizing	0.817	D	0.601	neutral	None	None	None	None	N
E/Q	0.15	likely_benign	0.1522	benign	-0.037	Destabilizing	0.006	N	0.193	neutral	N	0.47133865	None	None	N
E/R	0.3458	ambiguous	0.3674	ambiguous	0.681	Stabilizing	0.524	D	0.505	neutral	None	None	None	None	N
E/S	0.1815	likely_benign	0.1885	benign	-0.214	Destabilizing	0.239	N	0.434	neutral	None	None	None	None	N
E/T	0.1837	likely_benign	0.1924	benign	-0.069	Destabilizing	0.385	N	0.588	neutral	None	None	None	None	N
E/V	0.171	likely_benign	0.1776	benign	0.103	Stabilizing	0.624	D	0.645	neutral	N	0.480110835	None	None	N
E/W	0.9153	likely_pathogenic	0.9212	pathogenic	0.125	Stabilizing	0.981	D	0.823	deleterious	None	None	None	None	N
E/Y	0.571	likely_pathogenic	0.5852	pathogenic	0.24	Stabilizing	0.817	D	0.792	deleterious	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.