TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25384	76375;76376;76377	chr2:178569982;178569981;178569980	chr2:179434709;179434708;179434707
N2AB	23743	71452;71453;71454	chr2:178569982;178569981;178569980	chr2:179434709;179434708;179434707
N2A	22816	68671;68672;68673	chr2:178569982;178569981;178569980	chr2:179434709;179434708;179434707
N2B	16319	49180;49181;49182	chr2:178569982;178569981;178569980	chr2:179434709;179434708;179434707
Novex-1	16444	49555;49556;49557	chr2:178569982;178569981;178569980	chr2:179434709;179434708;179434707
Novex-2	16511	49756;49757;49758	chr2:178569982;178569981;178569980	chr2:179434709;179434708;179434707
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-72
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.5922
• 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
A/T	None	None	1.0	N	0.699	0.308	0.473538153929	gnomAD-4.0.0	2.73967E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.60086E-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
A/C	0.5456	ambiguous	0.6155	pathogenic	-0.844	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
A/D	0.539	ambiguous	0.5663	pathogenic	-0.474	Destabilizing	1.0	D	0.739	prob.delet.	D	0.522463256	None	None	I
A/E	0.3688	ambiguous	0.4008	ambiguous	-0.628	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
A/F	0.4079	ambiguous	0.449	ambiguous	-0.88	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
A/G	0.2251	likely_benign	0.2462	benign	-0.316	Destabilizing	1.0	D	0.528	neutral	N	0.46437321	None	None	I
A/H	0.5388	ambiguous	0.5915	pathogenic	-0.283	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
A/I	0.1936	likely_benign	0.2277	benign	-0.364	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
A/K	0.4133	ambiguous	0.445	ambiguous	-0.597	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
A/L	0.1518	likely_benign	0.1842	benign	-0.364	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
A/M	0.1858	likely_benign	0.2188	benign	-0.403	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
A/N	0.3255	likely_benign	0.3614	ambiguous	-0.346	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
A/P	0.5333	ambiguous	0.6183	pathogenic	-0.302	Destabilizing	1.0	D	0.715	prob.delet.	N	0.480473819	None	None	I
A/Q	0.3516	ambiguous	0.3951	ambiguous	-0.634	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
A/R	0.3932	ambiguous	0.3959	ambiguous	-0.112	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
A/S	0.1298	likely_benign	0.1402	benign	-0.553	Destabilizing	1.0	D	0.547	neutral	N	0.50522429	None	None	I
A/T	0.1023	likely_benign	0.1201	benign	-0.627	Destabilizing	1.0	D	0.699	prob.neutral	N	0.471266653	None	None	I
A/V	0.1108	likely_benign	0.1257	benign	-0.302	Destabilizing	1.0	D	0.631	neutral	N	0.47278759	None	None	I
A/W	0.8394	likely_pathogenic	0.8648	pathogenic	-0.996	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
A/Y	0.5682	likely_pathogenic	0.6069	pathogenic	-0.654	Destabilizing	1.0	D	0.715	prob.delet.	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.