TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8353	25282;25283;25284	chr2:178717949;178717948;178717947	chr2:179582676;179582675;179582674
N2AB	8036	24331;24332;24333	chr2:178717949;178717948;178717947	chr2:179582676;179582675;179582674
N2A	7109	21550;21551;21552	chr2:178717949;178717948;178717947	chr2:179582676;179582675;179582674
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-68
• Domain position: 90
• Structural Position: 177
• Q(SASA): 1.0303
• 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
I/N	None	None	0.994	N	0.589	0.638	0.888503533679	gnomAD-4.0.0	1.59872E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43612E-05	0
I/V	None	None	None	N	0.315	0.135	0.447803500395	gnomAD-4.0.0	1.37112E-06	None	None	None	None	I	None	0	4.48149E-05	None	0	0	None	0	0	0	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
I/A	0.5897	likely_pathogenic	0.6685	pathogenic	-1.712	Destabilizing	0.747	D	0.459	neutral	None	None	None	None	I
I/C	0.8194	likely_pathogenic	0.868	pathogenic	-0.902	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	I
I/D	0.9235	likely_pathogenic	0.9512	pathogenic	-1.422	Destabilizing	0.985	D	0.584	neutral	None	None	None	None	I
I/E	0.837	likely_pathogenic	0.881	pathogenic	-1.361	Destabilizing	0.98	D	0.59	neutral	None	None	None	None	I
I/F	0.3151	likely_benign	0.3841	ambiguous	-1.048	Destabilizing	0.908	D	0.485	neutral	N	0.504390739	None	None	I
I/G	0.8415	likely_pathogenic	0.8924	pathogenic	-2.069	Highly Destabilizing	0.014	N	0.368	neutral	None	None	None	None	I
I/H	0.8476	likely_pathogenic	0.8985	pathogenic	-1.201	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
I/K	0.7074	likely_pathogenic	0.7725	pathogenic	-1.298	Destabilizing	0.662	D	0.587	neutral	None	None	None	None	I
I/L	0.1466	likely_benign	0.184	benign	-0.77	Destabilizing	0.001	N	0.296	neutral	N	0.511457695	None	None	I
I/M	0.1371	likely_benign	0.1672	benign	-0.615	Destabilizing	0.912	D	0.497	neutral	N	0.504390739	None	None	I
I/N	0.5926	likely_pathogenic	0.683	pathogenic	-1.214	Destabilizing	0.994	D	0.589	neutral	N	0.516254024	None	None	I
I/P	0.8366	likely_pathogenic	0.8764	pathogenic	-1.056	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	I
I/Q	0.7438	likely_pathogenic	0.8094	pathogenic	-1.316	Destabilizing	0.997	D	0.583	neutral	None	None	None	None	I
I/R	0.6521	likely_pathogenic	0.7219	pathogenic	-0.733	Destabilizing	0.989	D	0.582	neutral	None	None	None	None	I
I/S	0.5923	likely_pathogenic	0.6724	pathogenic	-1.782	Destabilizing	0.961	D	0.535	neutral	N	0.516000534	None	None	I
I/T	0.4759	ambiguous	0.5632	ambiguous	-1.604	Destabilizing	0.754	D	0.509	neutral	N	0.50388376	None	None	I
I/V	0.0907	likely_benign	0.1008	benign	-1.056	Destabilizing	None	N	0.315	neutral	N	0.356052627	None	None	I
I/W	0.9013	likely_pathogenic	0.9299	pathogenic	-1.196	Destabilizing	1.0	D	0.576	neutral	None	None	None	None	I
I/Y	0.7572	likely_pathogenic	0.8098	pathogenic	-0.962	Destabilizing	0.916	D	0.567	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.