TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18869	56830;56831;56832	chr2:178599188;178599187;178599186	chr2:179463915;179463914;179463913
N2AB	17228	51907;51908;51909	chr2:178599188;178599187;178599186	chr2:179463915;179463914;179463913
N2A	16301	49126;49127;49128	chr2:178599188;178599187;178599186	chr2:179463915;179463914;179463913
N2B	9804	29635;29636;29637	chr2:178599188;178599187;178599186	chr2:179463915;179463914;179463913
Novex-1	9929	30010;30011;30012	chr2:178599188;178599187;178599186	chr2:179463915;179463914;179463913
Novex-2	9996	30211;30212;30213	chr2:178599188;178599187;178599186	chr2:179463915;179463914;179463913
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: Fn3-24
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.4661
• 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	0.891	N	0.473	0.193	0.343101102393	gnomAD-4.0.0	3.68E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.75148E-06	1.53619E-05	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	0.1698	likely_benign	0.1516	benign	-0.481	Destabilizing	0.625	D	0.497	neutral	N	0.517884156	None	None	N
E/C	0.8149	likely_pathogenic	0.7699	pathogenic	-0.211	Destabilizing	0.998	D	0.6	neutral	None	None	None	None	N
E/D	0.0881	likely_benign	0.0907	benign	-0.503	Destabilizing	0.012	N	0.094	neutral	N	0.465783254	None	None	N
E/F	0.6966	likely_pathogenic	0.6263	pathogenic	-0.274	Destabilizing	0.949	D	0.591	neutral	None	None	None	None	N
E/G	0.2299	likely_benign	0.1958	benign	-0.697	Destabilizing	0.891	D	0.585	neutral	N	0.484522289	None	None	N
E/H	0.5091	ambiguous	0.4371	ambiguous	-0.052	Destabilizing	0.991	D	0.549	neutral	None	None	None	None	N
E/I	0.2944	likely_benign	0.2515	benign	0.062	Stabilizing	0.904	D	0.611	neutral	None	None	None	None	N
E/K	0.1719	likely_benign	0.1375	benign	0.129	Stabilizing	0.891	D	0.473	neutral	N	0.496778165	None	None	N
E/L	0.3193	likely_benign	0.284	benign	0.062	Stabilizing	0.016	N	0.434	neutral	None	None	None	None	N
E/M	0.4009	ambiguous	0.3579	ambiguous	0.13	Stabilizing	0.949	D	0.582	neutral	None	None	None	None	N
E/N	0.2371	likely_benign	0.2193	benign	-0.219	Destabilizing	0.842	D	0.564	neutral	None	None	None	None	N
E/P	0.3485	ambiguous	0.2969	benign	-0.099	Destabilizing	0.007	N	0.18	neutral	None	None	None	None	N
E/Q	0.1575	likely_benign	0.1391	benign	-0.184	Destabilizing	0.891	D	0.577	neutral	N	0.491390988	None	None	N
E/R	0.3189	likely_benign	0.2541	benign	0.404	Stabilizing	0.974	D	0.58	neutral	None	None	None	None	N
E/S	0.2234	likely_benign	0.1994	benign	-0.389	Destabilizing	0.842	D	0.448	neutral	None	None	None	None	N
E/T	0.2592	likely_benign	0.2254	benign	-0.214	Destabilizing	0.915	D	0.548	neutral	None	None	None	None	N
E/V	0.1866	likely_benign	0.1614	benign	-0.099	Destabilizing	0.669	D	0.584	neutral	N	0.470914712	None	None	N
E/W	0.8899	likely_pathogenic	0.8429	pathogenic	-0.089	Destabilizing	0.998	D	0.663	neutral	None	None	None	None	N
E/Y	0.5588	ambiguous	0.4841	ambiguous	-0.028	Destabilizing	0.991	D	0.58	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.