TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16160	48703;48704;48705	chr2:178615467;178615466;178615465	chr2:179480194;179480193;179480192
N2AB	14519	43780;43781;43782	chr2:178615467;178615466;178615465	chr2:179480194;179480193;179480192
N2A	13592	40999;41000;41001	chr2:178615467;178615466;178615465	chr2:179480194;179480193;179480192
N2B	7095	21508;21509;21510	chr2:178615467;178615466;178615465	chr2:179480194;179480193;179480192
Novex-1	7220	21883;21884;21885	chr2:178615467;178615466;178615465	chr2:179480194;179480193;179480192
Novex-2	7287	22084;22085;22086	chr2:178615467;178615466;178615465	chr2:179480194;179480193;179480192
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-5
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.5306
• 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	rs1314919427	-0.897	0.999	N	0.637	0.37	0.447803500395	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
E/K	rs1314919427	-0.897	0.999	N	0.637	0.37	0.447803500395	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1314919427	-0.897	0.999	N	0.637	0.37	0.447803500395	gnomAD-4.0.0	4.96271E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93844E-06	0	1.60339E-05

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	0.2688	likely_benign	0.2813	benign	-0.664	Destabilizing	0.999	D	0.744	deleterious	N	0.483998192	None	None	N
E/C	0.8822	likely_pathogenic	0.8896	pathogenic	-0.492	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/D	0.31	likely_benign	0.3455	ambiguous	-1.199	Destabilizing	0.999	D	0.49	neutral	N	0.484156923	None	None	N
E/F	0.8916	likely_pathogenic	0.9037	pathogenic	-0.373	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/G	0.2743	likely_benign	0.2574	benign	-1.011	Destabilizing	1.0	D	0.801	deleterious	N	0.468212	None	None	N
E/H	0.748	likely_pathogenic	0.7596	pathogenic	-0.87	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/I	0.4837	ambiguous	0.5207	ambiguous	0.272	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
E/K	0.3305	likely_benign	0.2934	benign	-0.984	Destabilizing	0.999	D	0.637	neutral	N	0.482694897	None	None	N
E/L	0.5247	ambiguous	0.5747	pathogenic	0.272	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/M	0.6172	likely_pathogenic	0.6453	pathogenic	0.672	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/N	0.4859	ambiguous	0.5468	ambiguous	-1.2	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/P	0.9474	likely_pathogenic	0.9506	pathogenic	-0.019	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/Q	0.2025	likely_benign	0.2064	benign	-1.05	Destabilizing	1.0	D	0.66	neutral	N	0.473619222	None	None	N
E/R	0.4662	ambiguous	0.4177	ambiguous	-0.8	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/S	0.3287	likely_benign	0.3657	ambiguous	-1.506	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
E/T	0.3413	ambiguous	0.3792	ambiguous	-1.239	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/V	0.2925	likely_benign	0.3096	benign	-0.019	Destabilizing	1.0	D	0.844	deleterious	N	0.485298591	None	None	N
E/W	0.9603	likely_pathogenic	0.959	pathogenic	-0.317	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/Y	0.8301	likely_pathogenic	0.8408	pathogenic	-0.215	Destabilizing	1.0	D	0.85	deleterious	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.