TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25895	77908;77909;77910	chr2:178568449;178568448;178568447	chr2:179433176;179433175;179433174
N2AB	24254	72985;72986;72987	chr2:178568449;178568448;178568447	chr2:179433176;179433175;179433174
N2A	23327	70204;70205;70206	chr2:178568449;178568448;178568447	chr2:179433176;179433175;179433174
N2B	16830	50713;50714;50715	chr2:178568449;178568448;178568447	chr2:179433176;179433175;179433174
Novex-1	16955	51088;51089;51090	chr2:178568449;178568448;178568447	chr2:179433176;179433175;179433174
Novex-2	17022	51289;51290;51291	chr2:178568449;178568448;178568447	chr2:179433176;179433175;179433174
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-76
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.1884
• 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
K/E	rs1706799678	None	0.042	N	0.405	0.055	0.166414681773	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-06	0	0
K/T	rs751395038	-1.207	None	N	0.293	0.078	0.171388866994	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/T	rs751395038	-1.207	None	N	0.293	0.078	0.171388866994	gnomAD-4.0.0	3.18459E-06	None	None	None	None	N	None	0	2.28822E-05	None	0	0	None	0	0	2.85971E-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
K/A	0.1221	likely_benign	0.125	benign	-0.508	Destabilizing	0.025	N	0.357	neutral	None	None	None	None	N
K/C	0.2735	likely_benign	0.2626	benign	-0.417	Destabilizing	0.001	N	0.411	neutral	None	None	None	None	N
K/D	0.3995	ambiguous	0.418	ambiguous	-0.275	Destabilizing	0.22	N	0.486	neutral	None	None	None	None	N
K/E	0.0959	likely_benign	0.0965	benign	-0.142	Destabilizing	0.042	N	0.405	neutral	N	0.403894142	None	None	N
K/F	0.4772	ambiguous	0.4912	ambiguous	-0.006	Destabilizing	0.497	N	0.654	neutral	None	None	None	None	N
K/G	0.2264	likely_benign	0.2184	benign	-0.9	Destabilizing	0.104	N	0.452	neutral	None	None	None	None	N
K/H	0.2013	likely_benign	0.2	benign	-1.229	Destabilizing	0.497	N	0.489	neutral	None	None	None	None	N
K/I	0.1264	likely_benign	0.1221	benign	0.52	Stabilizing	0.042	N	0.478	neutral	N	0.496092227	None	None	N
K/L	0.152	likely_benign	0.1462	benign	0.52	Stabilizing	0.025	N	0.373	neutral	None	None	None	None	N
K/M	0.1077	likely_benign	0.104	benign	0.245	Stabilizing	0.667	D	0.505	neutral	None	None	None	None	N
K/N	0.2353	likely_benign	0.2394	benign	-0.541	Destabilizing	0.175	N	0.418	neutral	N	0.474236874	None	None	N
K/P	0.7669	likely_pathogenic	0.7837	pathogenic	0.207	Stabilizing	0.364	N	0.517	neutral	None	None	None	None	N
K/Q	0.0764	likely_benign	0.0729	benign	-0.494	Destabilizing	0.001	N	0.314	neutral	N	0.410340111	None	None	N
K/R	0.0738	likely_benign	0.0709	benign	-0.773	Destabilizing	None	N	0.211	neutral	N	0.442567173	None	None	N
K/S	0.1641	likely_benign	0.1632	benign	-1.069	Destabilizing	0.055	N	0.379	neutral	None	None	None	None	N
K/T	0.0719	likely_benign	0.0704	benign	-0.729	Destabilizing	None	N	0.293	neutral	N	0.381710715	None	None	N
K/V	0.0996	likely_benign	0.094	benign	0.207	Stabilizing	None	N	0.401	neutral	None	None	None	None	N
K/W	0.6198	likely_pathogenic	0.6154	pathogenic	0.036	Stabilizing	0.958	D	0.624	neutral	None	None	None	None	N
K/Y	0.3939	ambiguous	0.4104	ambiguous	0.291	Stabilizing	0.667	D	0.643	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.