TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25127	75604;75605;75606	chr2:178570753;178570752;178570751	chr2:179435480;179435479;179435478
N2AB	23486	70681;70682;70683	chr2:178570753;178570752;178570751	chr2:179435480;179435479;179435478
N2A	22559	67900;67901;67902	chr2:178570753;178570752;178570751	chr2:179435480;179435479;179435478
N2B	16062	48409;48410;48411	chr2:178570753;178570752;178570751	chr2:179435480;179435479;179435478
Novex-1	16187	48784;48785;48786	chr2:178570753;178570752;178570751	chr2:179435480;179435479;179435478
Novex-2	16254	48985;48986;48987	chr2:178570753;178570752;178570751	chr2:179435480;179435479;179435478
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-134
• Domain position: 17
• Structural Position: 25
• Q(SASA): 0.4896
• 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/G	rs768944134	-1.107	0.892	N	0.519	0.376	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/G	rs768944134	-1.107	0.892	N	0.519	0.376	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/G	rs768944134	-1.107	0.892	N	0.519	0.376	None	gnomAD-4.0.0	2.0301E-06	None	None	None	None	N	None	3.49565E-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	0.1833	likely_benign	0.2103	benign	-0.533	Destabilizing	0.892	D	0.514	neutral	N	0.468141737	None	None	N
E/C	0.819	likely_pathogenic	0.8617	pathogenic	-0.034	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
E/D	0.0934	likely_benign	0.094	benign	-0.584	Destabilizing	0.025	N	0.277	neutral	N	0.442260529	None	None	N
E/F	0.7767	likely_pathogenic	0.8311	pathogenic	-0.44	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/G	0.1809	likely_benign	0.2105	benign	-0.776	Destabilizing	0.892	D	0.519	neutral	N	0.485667376	None	None	N
E/H	0.495	ambiguous	0.5744	pathogenic	-0.491	Destabilizing	0.997	D	0.495	neutral	None	None	None	None	N
E/I	0.5116	ambiguous	0.5657	pathogenic	0.087	Stabilizing	0.987	D	0.719	prob.delet.	None	None	None	None	N
E/K	0.1916	likely_benign	0.2404	benign	0.027	Stabilizing	0.805	D	0.464	neutral	N	0.510621749	None	None	N
E/L	0.4976	ambiguous	0.563	ambiguous	0.087	Stabilizing	0.975	D	0.681	prob.neutral	None	None	None	None	N
E/M	0.4783	ambiguous	0.5434	ambiguous	0.39	Stabilizing	0.997	D	0.645	neutral	None	None	None	None	N
E/N	0.2245	likely_benign	0.2499	benign	-0.254	Destabilizing	0.975	D	0.475	neutral	None	None	None	None	N
E/P	0.9579	likely_pathogenic	0.9652	pathogenic	-0.099	Destabilizing	0.987	D	0.558	neutral	None	None	None	None	N
E/Q	0.1494	likely_benign	0.1787	benign	-0.203	Destabilizing	0.204	N	0.293	neutral	N	0.483704506	None	None	N
E/R	0.3451	ambiguous	0.4143	ambiguous	0.182	Stabilizing	0.95	D	0.489	neutral	None	None	None	None	N
E/S	0.1837	likely_benign	0.213	benign	-0.445	Destabilizing	0.916	D	0.482	neutral	None	None	None	None	N
E/T	0.2489	likely_benign	0.2914	benign	-0.253	Destabilizing	0.975	D	0.51	neutral	None	None	None	None	N
E/V	0.293	likely_benign	0.3337	benign	-0.099	Destabilizing	0.967	D	0.623	neutral	N	0.495907231	None	None	N
E/W	0.9297	likely_pathogenic	0.9541	pathogenic	-0.301	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
E/Y	0.6376	likely_pathogenic	0.7075	pathogenic	-0.21	Destabilizing	0.996	D	0.653	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.