TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6674	20245;20246;20247	chr2:178727345;178727344;178727343	chr2:179592072;179592071;179592070
N2AB	6357	19294;19295;19296	chr2:178727345;178727344;178727343	chr2:179592072;179592071;179592070
N2A	5430	16513;16514;16515	chr2:178727345;178727344;178727343	chr2:179592072;179592071;179592070
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-51
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.4736
• 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/Q	None	None	0.763	N	0.428	0.205	0.245660935333	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

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	0.2144	likely_benign	0.2227	benign	-0.448	Destabilizing	0.409	N	0.446	neutral	N	0.459339418	None	None	N
E/C	0.9345	likely_pathogenic	0.9315	pathogenic	-0.035	Destabilizing	0.987	D	0.662	neutral	None	None	None	None	N
E/D	0.102	likely_benign	0.0853	benign	-0.388	Destabilizing	None	N	0.101	neutral	N	0.486262022	None	None	N
E/F	0.879	likely_pathogenic	0.8697	pathogenic	-0.202	Destabilizing	0.974	D	0.611	neutral	None	None	None	None	N
E/G	0.2488	likely_benign	0.2531	benign	-0.674	Destabilizing	0.698	D	0.483	neutral	N	0.479089515	None	None	N
E/H	0.651	likely_pathogenic	0.6632	pathogenic	-0.066	Destabilizing	0.99	D	0.453	neutral	None	None	None	None	N
E/I	0.5906	likely_pathogenic	0.5839	pathogenic	0.122	Stabilizing	0.85	D	0.595	neutral	None	None	None	None	N
E/K	0.3578	ambiguous	0.3841	ambiguous	0.382	Stabilizing	0.562	D	0.417	neutral	N	0.494860076	None	None	N
E/L	0.561	ambiguous	0.5438	ambiguous	0.122	Stabilizing	0.85	D	0.589	neutral	None	None	None	None	N
E/M	0.697	likely_pathogenic	0.6958	pathogenic	0.276	Stabilizing	0.921	D	0.578	neutral	None	None	None	None	N
E/N	0.3836	ambiguous	0.3555	ambiguous	-0.093	Destabilizing	0.394	N	0.424	neutral	None	None	None	None	N
E/P	0.4428	ambiguous	0.4137	ambiguous	-0.047	Destabilizing	None	N	0.253	neutral	None	None	None	None	N
E/Q	0.235	likely_benign	0.2566	benign	-0.016	Destabilizing	0.763	D	0.428	neutral	N	0.484856513	None	None	N
E/R	0.4845	ambiguous	0.5195	ambiguous	0.551	Stabilizing	0.924	D	0.455	neutral	None	None	None	None	N
E/S	0.3109	likely_benign	0.2989	benign	-0.227	Destabilizing	0.315	N	0.394	neutral	None	None	None	None	N
E/T	0.3861	ambiguous	0.3808	ambiguous	-0.027	Destabilizing	0.559	D	0.457	neutral	None	None	None	None	N
E/V	0.3402	ambiguous	0.3441	ambiguous	-0.047	Destabilizing	0.752	D	0.524	neutral	N	0.501135474	None	None	N
E/W	0.948	likely_pathogenic	0.9502	pathogenic	0.002	Stabilizing	0.997	D	0.687	prob.neutral	None	None	None	None	N
E/Y	0.7837	likely_pathogenic	0.7822	pathogenic	0.06	Stabilizing	0.99	D	0.562	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.