TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18413	55462;55463;55464	chr2:178602034;178602033;178602032	chr2:179466761;179466760;179466759
N2AB	16772	50539;50540;50541	chr2:178602034;178602033;178602032	chr2:179466761;179466760;179466759
N2A	15845	47758;47759;47760	chr2:178602034;178602033;178602032	chr2:179466761;179466760;179466759
N2B	9348	28267;28268;28269	chr2:178602034;178602033;178602032	chr2:179466761;179466760;179466759
Novex-1	9473	28642;28643;28644	chr2:178602034;178602033;178602032	chr2:179466761;179466760;179466759
Novex-2	9540	28843;28844;28845	chr2:178602034;178602033;178602032	chr2:179466761;179466760;179466759
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-115
• Domain position: 32
• Structural Position: 49
• Q(SASA): 0.3173
• 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	rs2053599230	None	0.822	N	0.556	0.23	0.239305524855	gnomAD-4.0.0	1.36917E-06	None	None	None	None	N	None	5.9848E-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	0.1689	likely_benign	0.1639	benign	-0.843	Destabilizing	0.822	D	0.568	neutral	N	0.481469491	None	None	N
E/C	0.7367	likely_pathogenic	0.7143	pathogenic	-0.385	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
E/D	0.1831	likely_benign	0.2054	benign	-1.191	Destabilizing	0.006	N	0.272	neutral	N	0.481720207	None	None	N
E/F	0.6499	likely_pathogenic	0.6299	pathogenic	-0.613	Destabilizing	0.993	D	0.712	prob.delet.	None	None	None	None	N
E/G	0.271	likely_benign	0.2844	benign	-1.187	Destabilizing	0.822	D	0.617	neutral	N	0.481989566	None	None	N
E/H	0.4458	ambiguous	0.403	ambiguous	-0.964	Destabilizing	0.993	D	0.625	neutral	None	None	None	None	N
E/I	0.2525	likely_benign	0.2345	benign	0.089	Stabilizing	0.978	D	0.713	prob.delet.	None	None	None	None	N
E/K	0.2366	likely_benign	0.2133	benign	-0.498	Destabilizing	0.822	D	0.556	neutral	N	0.462363655	None	None	N
E/L	0.3796	ambiguous	0.3522	ambiguous	0.089	Stabilizing	0.978	D	0.697	prob.neutral	None	None	None	None	N
E/M	0.3746	ambiguous	0.3499	ambiguous	0.619	Stabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
E/N	0.2819	likely_benign	0.2756	benign	-0.912	Destabilizing	0.754	D	0.568	neutral	None	None	None	None	N
E/P	0.9853	likely_pathogenic	0.9895	pathogenic	-0.2	Destabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	N
E/Q	0.1412	likely_benign	0.1286	benign	-0.804	Destabilizing	0.822	D	0.562	neutral	N	0.454264247	None	None	N
E/R	0.3672	ambiguous	0.3263	benign	-0.388	Destabilizing	0.978	D	0.617	neutral	None	None	None	None	N
E/S	0.2074	likely_benign	0.1937	benign	-1.233	Destabilizing	0.86	D	0.556	neutral	None	None	None	None	N
E/T	0.1756	likely_benign	0.1685	benign	-0.939	Destabilizing	0.86	D	0.619	neutral	None	None	None	None	N
E/V	0.1539	likely_benign	0.144	benign	-0.2	Destabilizing	0.971	D	0.665	neutral	N	0.480949416	None	None	N
E/W	0.8931	likely_pathogenic	0.8924	pathogenic	-0.456	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
E/Y	0.5791	likely_pathogenic	0.5668	pathogenic	-0.365	Destabilizing	0.993	D	0.701	prob.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.