TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34292	103099;103100;103101	chr2:178533741;178533740;178533739	chr2:179398468;179398467;179398466
N2AB	32651	98176;98177;98178	chr2:178533741;178533740;178533739	chr2:179398468;179398467;179398466
N2A	31724	95395;95396;95397	chr2:178533741;178533740;178533739	chr2:179398468;179398467;179398466
N2B	25227	75904;75905;75906	chr2:178533741;178533740;178533739	chr2:179398468;179398467;179398466
Novex-1	25352	76279;76280;76281	chr2:178533741;178533740;178533739	chr2:179398468;179398467;179398466
Novex-2	25419	76480;76481;76482	chr2:178533741;178533740;178533739	chr2:179398468;179398467;179398466
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-161
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2188
• 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
Y/H	rs1690203448	None	0.989	N	0.548	0.267	0.331365685468	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/H	rs1690203448	None	0.989	N	0.548	0.267	0.331365685468	gnomAD-4.0.0	3.09828E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.3902E-06	0	1.60102E-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
Y/A	0.8616	likely_pathogenic	0.8916	pathogenic	-2.579	Highly Destabilizing	0.842	D	0.535	neutral	None	None	None	None	N
Y/C	0.2723	likely_benign	0.3621	ambiguous	-1.156	Destabilizing	0.997	D	0.606	neutral	N	0.470921262	None	None	N
Y/D	0.849	likely_pathogenic	0.8773	pathogenic	-1.159	Destabilizing	0.989	D	0.625	neutral	N	0.462527471	None	None	N
Y/E	0.8519	likely_pathogenic	0.8607	pathogenic	-1.053	Destabilizing	0.991	D	0.613	neutral	None	None	None	None	N
Y/F	0.0835	likely_benign	0.0825	benign	-1.086	Destabilizing	0.012	N	0.229	neutral	N	0.428933367	None	None	N
Y/G	0.8409	likely_pathogenic	0.8721	pathogenic	-2.908	Highly Destabilizing	0.974	D	0.617	neutral	None	None	None	None	N
Y/H	0.2611	likely_benign	0.2838	benign	-1.191	Destabilizing	0.989	D	0.548	neutral	N	0.504721992	None	None	N
Y/I	0.6353	likely_pathogenic	0.6665	pathogenic	-1.56	Destabilizing	0.525	D	0.481	neutral	None	None	None	None	N
Y/K	0.7711	likely_pathogenic	0.7854	pathogenic	-1.223	Destabilizing	0.974	D	0.608	neutral	None	None	None	None	N
Y/L	0.4116	ambiguous	0.4556	ambiguous	-1.56	Destabilizing	0.002	N	0.303	neutral	None	None	None	None	N
Y/M	0.5929	likely_pathogenic	0.6332	pathogenic	-1.215	Destabilizing	0.949	D	0.581	neutral	None	None	None	None	N
Y/N	0.493	ambiguous	0.5389	ambiguous	-1.504	Destabilizing	0.989	D	0.612	neutral	N	0.442448207	None	None	N
Y/P	0.9977	likely_pathogenic	0.9985	pathogenic	-1.898	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	N
Y/Q	0.6983	likely_pathogenic	0.7328	pathogenic	-1.47	Destabilizing	0.991	D	0.573	neutral	None	None	None	None	N
Y/R	0.6514	likely_pathogenic	0.6706	pathogenic	-0.73	Destabilizing	0.974	D	0.609	neutral	None	None	None	None	N
Y/S	0.589	likely_pathogenic	0.6397	pathogenic	-2.13	Highly Destabilizing	0.891	D	0.605	neutral	N	0.497390588	None	None	N
Y/T	0.7292	likely_pathogenic	0.7736	pathogenic	-1.93	Destabilizing	0.915	D	0.581	neutral	None	None	None	None	N
Y/V	0.5855	likely_pathogenic	0.6397	pathogenic	-1.898	Destabilizing	0.525	D	0.487	neutral	None	None	None	None	N
Y/W	0.4589	ambiguous	0.4454	ambiguous	-0.52	Destabilizing	0.991	D	0.548	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.