TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26308	79147;79148;79149	chr2:178567210;178567209;178567208	chr2:179431937;179431936;179431935
N2AB	24667	74224;74225;74226	chr2:178567210;178567209;178567208	chr2:179431937;179431936;179431935
N2A	23740	71443;71444;71445	chr2:178567210;178567209;178567208	chr2:179431937;179431936;179431935
N2B	17243	51952;51953;51954	chr2:178567210;178567209;178567208	chr2:179431937;179431936;179431935
Novex-1	17368	52327;52328;52329	chr2:178567210;178567209;178567208	chr2:179431937;179431936;179431935
Novex-2	17435	52528;52529;52530	chr2:178567210;178567209;178567208	chr2:179431937;179431936;179431935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-79
• Domain position: 23
• Structural Position: 24
• Q(SASA): 0.0954
• 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
W/S	rs1201085993	-3.363	0.967	D	0.897	0.758	0.936706721517	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
W/S	rs1201085993	-3.363	0.967	D	0.897	0.758	0.936706721517	gnomAD-4.0.0	1.59931E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87285E-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
W/A	0.9971	likely_pathogenic	0.9972	pathogenic	-3.256	Highly Destabilizing	0.845	D	0.881	deleterious	None	None	None	None	N
W/C	0.9986	likely_pathogenic	0.9987	pathogenic	-2.045	Highly Destabilizing	0.056	N	0.722	prob.delet.	D	0.679411529	None	None	N
W/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.751	Highly Destabilizing	0.996	D	0.891	deleterious	None	None	None	None	N
W/E	0.9999	likely_pathogenic	0.9999	pathogenic	-3.623	Highly Destabilizing	0.996	D	0.901	deleterious	None	None	None	None	N
W/F	0.7086	likely_pathogenic	0.734	pathogenic	-2.081	Highly Destabilizing	0.987	D	0.807	deleterious	None	None	None	None	N
W/G	0.9891	likely_pathogenic	0.9897	pathogenic	-3.514	Highly Destabilizing	0.983	D	0.851	deleterious	D	0.679411529	None	None	N
W/H	0.9984	likely_pathogenic	0.9987	pathogenic	-2.723	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
W/I	0.9934	likely_pathogenic	0.9936	pathogenic	-2.264	Highly Destabilizing	0.975	D	0.906	deleterious	None	None	None	None	N
W/K	0.9999	likely_pathogenic	0.9999	pathogenic	-2.832	Highly Destabilizing	0.987	D	0.899	deleterious	None	None	None	None	N
W/L	0.9872	likely_pathogenic	0.9879	pathogenic	-2.264	Highly Destabilizing	0.805	D	0.855	deleterious	D	0.678200703	None	None	N
W/M	0.9975	likely_pathogenic	0.9976	pathogenic	-1.823	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
W/N	0.9998	likely_pathogenic	0.9998	pathogenic	-3.593	Highly Destabilizing	0.996	D	0.907	deleterious	None	None	None	None	N
W/P	0.9995	likely_pathogenic	0.9996	pathogenic	-2.627	Highly Destabilizing	0.996	D	0.907	deleterious	None	None	None	None	N
W/Q	0.9999	likely_pathogenic	0.9999	pathogenic	-3.372	Highly Destabilizing	0.996	D	0.887	deleterious	None	None	None	None	N
W/R	0.9997	likely_pathogenic	0.9997	pathogenic	-2.64	Highly Destabilizing	0.994	D	0.903	deleterious	D	0.679411529	None	None	N
W/S	0.9966	likely_pathogenic	0.9969	pathogenic	-3.701	Highly Destabilizing	0.967	D	0.897	deleterious	D	0.663392168	None	None	N
W/T	0.9986	likely_pathogenic	0.9987	pathogenic	-3.492	Highly Destabilizing	0.975	D	0.85	deleterious	None	None	None	None	N
W/V	0.9928	likely_pathogenic	0.9933	pathogenic	-2.627	Highly Destabilizing	0.975	D	0.892	deleterious	None	None	None	None	N
W/Y	0.9503	likely_pathogenic	0.9609	pathogenic	-1.965	Destabilizing	0.996	D	0.803	deleterious	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.