TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25649	77170;77171;77172	chr2:178569187;178569186;178569185	chr2:179433914;179433913;179433912
N2AB	24008	72247;72248;72249	chr2:178569187;178569186;178569185	chr2:179433914;179433913;179433912
N2A	23081	69466;69467;69468	chr2:178569187;178569186;178569185	chr2:179433914;179433913;179433912
N2B	16584	49975;49976;49977	chr2:178569187;178569186;178569185	chr2:179433914;179433913;179433912
Novex-1	16709	50350;50351;50352	chr2:178569187;178569186;178569185	chr2:179433914;179433913;179433912
Novex-2	16776	50551;50552;50553	chr2:178569187;178569186;178569185	chr2:179433914;179433913;179433912
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-74
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.3367
• 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
A/T	None	None	0.805	N	0.447	0.11	0.207176502487	gnomAD-4.0.0	1.37102E-06	None	None	None	None	N	None	3.00012E-05	0	None	0	0	None	0	0	9.0043E-07	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
A/C	0.5568	ambiguous	0.5612	ambiguous	-0.852	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
A/D	0.8383	likely_pathogenic	0.839	pathogenic	-0.585	Destabilizing	0.967	D	0.561	neutral	N	0.516670648	None	None	N
A/E	0.7593	likely_pathogenic	0.7511	pathogenic	-0.685	Destabilizing	0.916	D	0.517	neutral	None	None	None	None	N
A/F	0.5462	ambiguous	0.5691	pathogenic	-0.95	Destabilizing	0.987	D	0.687	prob.neutral	None	None	None	None	N
A/G	0.2524	likely_benign	0.2545	benign	-0.816	Destabilizing	0.63	D	0.488	neutral	N	0.51465185	None	None	N
A/H	0.7594	likely_pathogenic	0.7567	pathogenic	-0.756	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
A/I	0.331	likely_benign	0.3487	ambiguous	-0.455	Destabilizing	0.987	D	0.629	neutral	None	None	None	None	N
A/K	0.8887	likely_pathogenic	0.8901	pathogenic	-0.935	Destabilizing	0.916	D	0.508	neutral	None	None	None	None	N
A/L	0.2493	likely_benign	0.257	benign	-0.455	Destabilizing	0.916	D	0.513	neutral	None	None	None	None	N
A/M	0.2736	likely_benign	0.2764	benign	-0.482	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
A/N	0.4733	ambiguous	0.4806	ambiguous	-0.647	Destabilizing	0.975	D	0.566	neutral	None	None	None	None	N
A/P	0.9114	likely_pathogenic	0.9197	pathogenic	-0.489	Destabilizing	0.983	D	0.629	neutral	N	0.46584860299999997	None	None	N
A/Q	0.621	likely_pathogenic	0.6132	pathogenic	-0.882	Destabilizing	0.975	D	0.648	neutral	None	None	None	None	N
A/R	0.8533	likely_pathogenic	0.8579	pathogenic	-0.473	Destabilizing	0.975	D	0.638	neutral	None	None	None	None	N
A/S	0.1004	likely_benign	0.1002	benign	-0.946	Destabilizing	0.044	N	0.238	neutral	N	0.407484312	None	None	N
A/T	0.0943	likely_benign	0.093	benign	-0.959	Destabilizing	0.805	D	0.447	neutral	N	0.416450512	None	None	N
A/V	0.1512	likely_benign	0.1601	benign	-0.489	Destabilizing	0.892	D	0.491	neutral	N	0.45135252	None	None	N
A/W	0.9342	likely_pathogenic	0.9359	pathogenic	-1.134	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
A/Y	0.7485	likely_pathogenic	0.7562	pathogenic	-0.783	Destabilizing	0.996	D	0.675	prob.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.