TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3396	10411;10412;10413	chr2:178759101;178759100;178759099	chr2:179623828;179623827;179623826
N2AB	3396	10411;10412;10413	chr2:178759101;178759100;178759099	chr2:179623828;179623827;179623826
N2A	3396	10411;10412;10413	chr2:178759101;178759100;178759099	chr2:179623828;179623827;179623826
N2B	3350	10273;10274;10275	chr2:178759101;178759100;178759099	chr2:179623828;179623827;179623826
Novex-1	3350	10273;10274;10275	chr2:178759101;178759100;178759099	chr2:179623828;179623827;179623826
Novex-2	3350	10273;10274;10275	chr2:178759101;178759100;178759099	chr2:179623828;179623827;179623826
Novex-3	3396	10411;10412;10413	chr2:178759101;178759100;178759099	chr2:179623828;179623827;179623826

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-24
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.6542
• 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	0.961	N	0.385	0.517	0.48087575253	gnomAD-4.0.0	6.84111E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99332E-07	0	0
E/Q	None	None	0.994	N	0.32	0.449	0.379193981924	gnomAD-4.0.0	6.84111E-07	None	None	None	None	N	None	0	0	None	0	2.5208E-05	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	0.3174	likely_benign	0.3759	ambiguous	-0.309	Destabilizing	0.961	D	0.408	neutral	N	0.518155459	None	None	N
E/C	0.9642	likely_pathogenic	0.9578	pathogenic	-0.218	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	N
E/D	0.2338	likely_benign	0.2792	benign	-0.274	Destabilizing	0.031	N	0.181	neutral	N	0.4802842	None	None	N
E/F	0.956	likely_pathogenic	0.9607	pathogenic	-0.156	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	N
E/G	0.2134	likely_benign	0.2412	benign	-0.477	Destabilizing	0.961	D	0.377	neutral	N	0.413338828	None	None	N
E/H	0.7558	likely_pathogenic	0.7956	pathogenic	0.31	Stabilizing	1.0	D	0.333	neutral	None	None	None	None	N
E/I	0.8489	likely_pathogenic	0.8657	pathogenic	0.094	Stabilizing	0.983	D	0.472	neutral	None	None	None	None	N
E/K	0.2639	likely_benign	0.3122	benign	0.308	Stabilizing	0.961	D	0.385	neutral	N	0.514913952	None	None	N
E/L	0.744	likely_pathogenic	0.7651	pathogenic	0.094	Stabilizing	0.942	D	0.439	neutral	None	None	None	None	N
E/M	0.8	likely_pathogenic	0.8151	pathogenic	0.017	Stabilizing	0.999	D	0.465	neutral	None	None	None	None	N
E/N	0.502	ambiguous	0.5933	pathogenic	-0.056	Destabilizing	0.991	D	0.297	neutral	None	None	None	None	N
E/P	0.792	likely_pathogenic	0.8516	pathogenic	-0.022	Destabilizing	0.999	D	0.362	neutral	None	None	None	None	N
E/Q	0.2436	likely_benign	0.2912	benign	-0.003	Destabilizing	0.994	D	0.32	neutral	N	0.519538411	None	None	N
E/R	0.4007	ambiguous	0.444	ambiguous	0.585	Stabilizing	0.996	D	0.327	neutral	None	None	None	None	N
E/S	0.3629	ambiguous	0.4297	ambiguous	-0.2	Destabilizing	0.97	D	0.363	neutral	None	None	None	None	N
E/T	0.5722	likely_pathogenic	0.6431	pathogenic	-0.051	Destabilizing	0.97	D	0.363	neutral	None	None	None	None	N
E/V	0.6706	likely_pathogenic	0.7002	pathogenic	-0.022	Destabilizing	0.433	N	0.341	neutral	D	0.557141709	None	None	N
E/W	0.9757	likely_pathogenic	0.9738	pathogenic	-0.009	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
E/Y	0.8986	likely_pathogenic	0.9065	pathogenic	0.084	Stabilizing	0.999	D	0.447	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.