TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31097	93514;93515;93516	chr2:178548337;178548336;178548335	chr2:179413064;179413063;179413062
N2AB	29456	88591;88592;88593	chr2:178548337;178548336;178548335	chr2:179413064;179413063;179413062
N2A	28529	85810;85811;85812	chr2:178548337;178548336;178548335	chr2:179413064;179413063;179413062
N2B	22032	66319;66320;66321	chr2:178548337;178548336;178548335	chr2:179413064;179413063;179413062
Novex-1	22157	66694;66695;66696	chr2:178548337;178548336;178548335	chr2:179413064;179413063;179413062
Novex-2	22224	66895;66896;66897	chr2:178548337;178548336;178548335	chr2:179413064;179413063;179413062
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-114
• Domain position: 82
• Structural Position: 115
• Q(SASA): 0.1915
• 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
G/D	rs879219987	-0.744	1.0	D	0.92	0.756	0.584736501517	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
G/D	rs879219987	-0.744	1.0	D	0.92	0.756	0.584736501517	gnomAD-4.0.0	1.59113E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02389E-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
G/A	0.8107	likely_pathogenic	0.7682	pathogenic	-0.578	Destabilizing	1.0	D	0.763	deleterious	D	0.575627719	None	None	I
G/C	0.9329	likely_pathogenic	0.9036	pathogenic	-0.967	Destabilizing	1.0	D	0.879	deleterious	D	0.576895167	None	None	I
G/D	0.9401	likely_pathogenic	0.9119	pathogenic	-0.917	Destabilizing	1.0	D	0.92	deleterious	D	0.565031882	None	None	I
G/E	0.9721	likely_pathogenic	0.9526	pathogenic	-1.059	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	I
G/F	0.9924	likely_pathogenic	0.9898	pathogenic	-1.136	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
G/H	0.9801	likely_pathogenic	0.9697	pathogenic	-0.849	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
G/I	0.9882	likely_pathogenic	0.9814	pathogenic	-0.57	Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	I
G/K	0.9837	likely_pathogenic	0.9742	pathogenic	-1.164	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
G/L	0.9802	likely_pathogenic	0.9752	pathogenic	-0.57	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/M	0.9891	likely_pathogenic	0.9848	pathogenic	-0.504	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
G/N	0.9599	likely_pathogenic	0.9448	pathogenic	-0.798	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/P	0.9981	likely_pathogenic	0.9976	pathogenic	-0.536	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	I
G/Q	0.9676	likely_pathogenic	0.9502	pathogenic	-1.095	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	I
G/R	0.9496	likely_pathogenic	0.9213	pathogenic	-0.651	Destabilizing	1.0	D	0.918	deleterious	D	0.564778393	None	None	I
G/S	0.6505	likely_pathogenic	0.5948	pathogenic	-0.966	Destabilizing	1.0	D	0.861	deleterious	D	0.557434559	None	None	I
G/T	0.9345	likely_pathogenic	0.9068	pathogenic	-1.042	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	I
G/V	0.9772	likely_pathogenic	0.965	pathogenic	-0.536	Destabilizing	1.0	D	0.895	deleterious	D	0.546167159	None	None	I
G/W	0.9876	likely_pathogenic	0.9799	pathogenic	-1.311	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/Y	0.9862	likely_pathogenic	0.9805	pathogenic	-0.979	Destabilizing	1.0	D	0.899	deleterious	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.