TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25903	77932;77933;77934	chr2:178568425;178568424;178568423	chr2:179433152;179433151;179433150
N2AB	24262	73009;73010;73011	chr2:178568425;178568424;178568423	chr2:179433152;179433151;179433150
N2A	23335	70228;70229;70230	chr2:178568425;178568424;178568423	chr2:179433152;179433151;179433150
N2B	16838	50737;50738;50739	chr2:178568425;178568424;178568423	chr2:179433152;179433151;179433150
Novex-1	16963	51112;51113;51114	chr2:178568425;178568424;178568423	chr2:179433152;179433151;179433150
Novex-2	17030	51313;51314;51315	chr2:178568425;178568424;178568423	chr2:179433152;179433151;179433150
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-76
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.42
• 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
V/D	rs764027734	-0.209	0.667	D	0.719	0.508	0.798081691357	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	8.9E-06	0
V/D	rs764027734	-0.209	0.667	D	0.719	0.508	0.798081691357	gnomAD-4.0.0	1.27397E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14391E-05	5.7323E-05	0
V/G	None	None	0.667	N	0.699	0.502	0.769505205396	gnomAD-4.0.0	1.59247E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85977E-06	0	0
V/I	rs570615498	-0.49	0.002	N	0.138	0.085	None	gnomAD-2.1.1	1.46659E-04	None	None	None	None	N	None	1.65426E-04	8.51E-05	None	0	5.17E-05	None	9.81E-05	None	1.20144E-04	2.11248E-04	0
V/I	rs570615498	-0.49	0.002	N	0.138	0.085	None	gnomAD-3.1.2	8.55E-05	None	None	None	None	N	None	1.20802E-04	1.31216E-04	0	0	0	None	3.77216E-04	0	2.94E-05	0	0
V/I	rs570615498	-0.49	0.002	N	0.138	0.085	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
V/I	rs570615498	-0.49	0.002	N	0.138	0.085	None	gnomAD-4.0.0	8.80262E-05	None	None	None	None	N	None	9.33881E-05	1.00113E-04	None	3.37929E-05	0	None	7.81983E-05	0	9.57994E-05	7.68724E-05	4.8043E-05
V/L	None	None	0.022	N	0.298	0.134	0.355242300401	gnomAD-4.0.0	1.36888E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79925E-06	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
V/A	0.4596	ambiguous	0.5676	pathogenic	-1.665	Destabilizing	0.104	N	0.493	neutral	N	0.48973021	None	None	N
V/C	0.7763	likely_pathogenic	0.8134	pathogenic	-1.73	Destabilizing	0.968	D	0.563	neutral	None	None	None	None	N
V/D	0.8465	likely_pathogenic	0.913	pathogenic	-1.145	Destabilizing	0.667	D	0.719	prob.delet.	D	0.529990872	None	None	N
V/E	0.7229	likely_pathogenic	0.8139	pathogenic	-1.062	Destabilizing	0.726	D	0.663	neutral	None	None	None	None	N
V/F	0.3014	likely_benign	0.4104	ambiguous	-1.279	Destabilizing	0.715	D	0.573	neutral	N	0.482870583	None	None	N
V/G	0.6394	likely_pathogenic	0.7274	pathogenic	-2.047	Highly Destabilizing	0.667	D	0.699	prob.neutral	N	0.519648524	None	None	N
V/H	0.8478	likely_pathogenic	0.9043	pathogenic	-1.577	Destabilizing	0.968	D	0.724	prob.delet.	None	None	None	None	N
V/I	0.0602	likely_benign	0.0594	benign	-0.681	Destabilizing	0.002	N	0.138	neutral	N	0.490409553	None	None	N
V/K	0.6504	likely_pathogenic	0.7194	pathogenic	-1.168	Destabilizing	0.726	D	0.673	neutral	None	None	None	None	N
V/L	0.2706	likely_benign	0.3308	benign	-0.681	Destabilizing	0.022	N	0.298	neutral	N	0.474562016	None	None	N
V/M	0.2184	likely_benign	0.2616	benign	-0.878	Destabilizing	0.567	D	0.483	neutral	None	None	None	None	N
V/N	0.6454	likely_pathogenic	0.7615	pathogenic	-1.158	Destabilizing	0.89	D	0.719	prob.delet.	None	None	None	None	N
V/P	0.8957	likely_pathogenic	0.9164	pathogenic	-0.976	Destabilizing	0.89	D	0.668	neutral	None	None	None	None	N
V/Q	0.6769	likely_pathogenic	0.759	pathogenic	-1.208	Destabilizing	0.89	D	0.677	prob.neutral	None	None	None	None	N
V/R	0.6099	likely_pathogenic	0.6886	pathogenic	-0.882	Destabilizing	0.726	D	0.718	prob.delet.	None	None	None	None	N
V/S	0.5663	likely_pathogenic	0.6854	pathogenic	-1.897	Destabilizing	0.726	D	0.579	neutral	None	None	None	None	N
V/T	0.3719	ambiguous	0.4493	ambiguous	-1.677	Destabilizing	0.272	N	0.453	neutral	None	None	None	None	N
V/W	0.934	likely_pathogenic	0.9582	pathogenic	-1.446	Destabilizing	0.968	D	0.734	prob.delet.	None	None	None	None	N
V/Y	0.7316	likely_pathogenic	0.8284	pathogenic	-1.112	Destabilizing	0.726	D	0.578	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.