TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23786	71581;71582;71583	chr2:178574776;178574775;178574774	chr2:179439503;179439502;179439501
N2AB	22145	66658;66659;66660	chr2:178574776;178574775;178574774	chr2:179439503;179439502;179439501
N2A	21218	63877;63878;63879	chr2:178574776;178574775;178574774	chr2:179439503;179439502;179439501
N2B	14721	44386;44387;44388	chr2:178574776;178574775;178574774	chr2:179439503;179439502;179439501
Novex-1	14846	44761;44762;44763	chr2:178574776;178574775;178574774	chr2:179439503;179439502;179439501
Novex-2	14913	44962;44963;44964	chr2:178574776;178574775;178574774	chr2:179439503;179439502;179439501
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: Fn3-60
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.4108
• Predicted PPI site: I

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/C	rs758011912	-1.162	0.997	N	0.585	0.418	0.53782465974	gnomAD-2.1.1	8.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.59E-05	None	0	0	0
Y/C	rs758011912	-1.162	0.997	N	0.585	0.418	0.53782465974	gnomAD-4.0.0	3.42477E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	5.81058E-05	0
Y/H	None	None	0.989	N	0.487	0.488	0.447213685739	gnomAD-4.0.0	1.59516E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.03232E-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	0.9035	likely_pathogenic	0.8677	pathogenic	-2.046	Highly Destabilizing	0.915	D	0.505	neutral	None	None	None	None	I
Y/C	0.2105	likely_benign	0.1713	benign	-1.417	Destabilizing	0.997	D	0.585	neutral	N	0.451683381	None	None	I
Y/D	0.9831	likely_pathogenic	0.9708	pathogenic	-2.276	Highly Destabilizing	0.989	D	0.583	neutral	N	0.50954644	None	None	I
Y/E	0.9883	likely_pathogenic	0.983	pathogenic	-2.075	Highly Destabilizing	0.991	D	0.567	neutral	None	None	None	None	I
Y/F	0.0658	likely_benign	0.0558	benign	-0.588	Destabilizing	0.002	N	0.171	neutral	N	0.407833816	None	None	I
Y/G	0.911	likely_pathogenic	0.8851	pathogenic	-2.436	Highly Destabilizing	0.915	D	0.529	neutral	None	None	None	None	I
Y/H	0.7151	likely_pathogenic	0.6577	pathogenic	-1.206	Destabilizing	0.989	D	0.487	neutral	N	0.506632586	None	None	I
Y/I	0.6788	likely_pathogenic	0.6209	pathogenic	-0.788	Destabilizing	0.728	D	0.424	neutral	None	None	None	None	I
Y/K	0.9751	likely_pathogenic	0.9663	pathogenic	-1.804	Destabilizing	0.991	D	0.568	neutral	None	None	None	None	I
Y/L	0.6658	likely_pathogenic	0.634	pathogenic	-0.788	Destabilizing	0.525	D	0.478	neutral	None	None	None	None	I
Y/M	0.7409	likely_pathogenic	0.6939	pathogenic	-0.721	Destabilizing	0.974	D	0.52	neutral	None	None	None	None	I
Y/N	0.8969	likely_pathogenic	0.851	pathogenic	-2.647	Highly Destabilizing	0.989	D	0.573	neutral	N	0.497936645	None	None	I
Y/P	0.9963	likely_pathogenic	0.9947	pathogenic	-1.215	Destabilizing	0.991	D	0.588	neutral	None	None	None	None	I
Y/Q	0.9571	likely_pathogenic	0.9403	pathogenic	-2.297	Highly Destabilizing	0.991	D	0.525	neutral	None	None	None	None	I
Y/R	0.9457	likely_pathogenic	0.9315	pathogenic	-1.832	Destabilizing	0.991	D	0.577	neutral	None	None	None	None	I
Y/S	0.8476	likely_pathogenic	0.7886	pathogenic	-3.004	Highly Destabilizing	0.891	D	0.523	neutral	N	0.482541415	None	None	I
Y/T	0.9098	likely_pathogenic	0.8691	pathogenic	-2.677	Highly Destabilizing	0.915	D	0.539	neutral	None	None	None	None	I
Y/V	0.5963	likely_pathogenic	0.5243	ambiguous	-1.215	Destabilizing	0.842	D	0.433	neutral	None	None	None	None	I
Y/W	0.5111	ambiguous	0.4798	ambiguous	-0.051	Destabilizing	0.991	D	0.478	neutral	None	None	None	None	I

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.