TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18313	55162;55163;55164	chr2:178602465;178602464;178602463	chr2:179467192;179467191;179467190
N2AB	16672	50239;50240;50241	chr2:178602465;178602464;178602463	chr2:179467192;179467191;179467190
N2A	15745	47458;47459;47460	chr2:178602465;178602464;178602463	chr2:179467192;179467191;179467190
N2B	9248	27967;27968;27969	chr2:178602465;178602464;178602463	chr2:179467192;179467191;179467190
Novex-1	9373	28342;28343;28344	chr2:178602465;178602464;178602463	chr2:179467192;179467191;179467190
Novex-2	9440	28543;28544;28545	chr2:178602465;178602464;178602463	chr2:179467192;179467191;179467190
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: Fn3-21
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3873
• 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/D	rs751397444	-1.152	0.004	N	0.129	0.01	0.124217242631	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	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	0.1976	likely_benign	0.1884	benign	-0.756	Destabilizing	0.896	D	0.521	neutral	N	0.477675888	None	None	N
E/C	0.8482	likely_pathogenic	0.8705	pathogenic	-0.47	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/D	0.1922	likely_benign	0.2315	benign	-1.138	Destabilizing	0.004	N	0.129	neutral	N	0.468727559	None	None	N
E/F	0.8327	likely_pathogenic	0.8637	pathogenic	-0.236	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
E/G	0.2481	likely_benign	0.2858	benign	-1.129	Destabilizing	0.896	D	0.565	neutral	N	0.477866926	None	None	N
E/H	0.6877	likely_pathogenic	0.7202	pathogenic	-0.634	Destabilizing	0.996	D	0.555	neutral	None	None	None	None	N
E/I	0.4071	ambiguous	0.3871	ambiguous	0.26	Stabilizing	0.988	D	0.727	prob.delet.	None	None	None	None	N
E/K	0.2944	likely_benign	0.275	benign	-0.773	Destabilizing	0.896	D	0.477	neutral	N	0.491929706	None	None	N
E/L	0.4194	ambiguous	0.4031	ambiguous	0.26	Stabilizing	0.988	D	0.683	prob.neutral	None	None	None	None	N
E/M	0.4935	ambiguous	0.4757	ambiguous	0.68	Stabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	N
E/N	0.4224	ambiguous	0.4863	ambiguous	-1.155	Destabilizing	0.851	D	0.487	neutral	None	None	None	None	N
E/P	0.459	ambiguous	0.4484	ambiguous	-0.057	Destabilizing	0.988	D	0.583	neutral	None	None	None	None	N
E/Q	0.226	likely_benign	0.2134	benign	-0.991	Destabilizing	0.946	D	0.483	neutral	N	0.467013918	None	None	N
E/R	0.4434	ambiguous	0.4381	ambiguous	-0.527	Destabilizing	0.988	D	0.542	neutral	None	None	None	None	N
E/S	0.3347	likely_benign	0.3763	ambiguous	-1.471	Destabilizing	0.919	D	0.463	neutral	None	None	None	None	N
E/T	0.341	ambiguous	0.3438	ambiguous	-1.167	Destabilizing	0.959	D	0.534	neutral	None	None	None	None	N
E/V	0.2249	likely_benign	0.2129	benign	-0.057	Destabilizing	0.984	D	0.601	neutral	N	0.481816945	None	None	N
E/W	0.9267	likely_pathogenic	0.9389	pathogenic	-0.05	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
E/Y	0.743	likely_pathogenic	0.7843	pathogenic	-0.021	Destabilizing	0.996	D	0.713	prob.delet.	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.