TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7397	22414;22415;22416	chr2:178722710;178722709;178722708	chr2:179587437;179587436;179587435
N2AB	7080	21463;21464;21465	chr2:178722710;178722709;178722708	chr2:179587437;179587436;179587435
N2A	6153	18682;18683;18684	chr2:178722710;178722709;178722708	chr2:179587437;179587436;179587435
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-58
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0926
• 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
A/T	rs1444697526	-1.808	1.0	D	0.644	0.555	0.525922550829	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
A/T	rs1444697526	-1.808	1.0	D	0.644	0.555	0.525922550829	gnomAD-4.0.0	1.59296E-06	None	None	None	None	N	None	0	2.28969E-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
A/C	0.9241	likely_pathogenic	0.9446	pathogenic	-1.875	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
A/D	0.9954	likely_pathogenic	0.9986	pathogenic	-2.675	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
A/E	0.9881	likely_pathogenic	0.9956	pathogenic	-2.536	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.644835098	None	None	N
A/F	0.9598	likely_pathogenic	0.9834	pathogenic	-1.064	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
A/G	0.3701	ambiguous	0.4812	ambiguous	-1.893	Destabilizing	0.979	D	0.622	neutral	D	0.596343047	None	None	N
A/H	0.9973	likely_pathogenic	0.9991	pathogenic	-1.86	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
A/I	0.8152	likely_pathogenic	0.8748	pathogenic	-0.433	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
A/K	0.9981	likely_pathogenic	0.9994	pathogenic	-1.513	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
A/L	0.7274	likely_pathogenic	0.7848	pathogenic	-0.433	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
A/M	0.8429	likely_pathogenic	0.9077	pathogenic	-0.799	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
A/N	0.9928	likely_pathogenic	0.9974	pathogenic	-1.756	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
A/P	0.9926	likely_pathogenic	0.997	pathogenic	-0.745	Destabilizing	1.0	D	0.842	deleterious	D	0.628583573	None	None	N
A/Q	0.9887	likely_pathogenic	0.9951	pathogenic	-1.72	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/R	0.9918	likely_pathogenic	0.9967	pathogenic	-1.357	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/S	0.5291	ambiguous	0.6398	pathogenic	-2.19	Highly Destabilizing	0.99	D	0.334	neutral	D	0.607052981	None	None	N
A/T	0.6297	likely_pathogenic	0.7582	pathogenic	-1.938	Destabilizing	1.0	D	0.644	neutral	D	0.595939438	None	None	N
A/V	0.4846	ambiguous	0.5594	ambiguous	-0.745	Destabilizing	0.982	D	0.367	neutral	N	0.508278306	None	None	N
A/W	0.9968	likely_pathogenic	0.9991	pathogenic	-1.586	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
A/Y	0.9896	likely_pathogenic	0.9965	pathogenic	-1.16	Destabilizing	1.0	D	0.874	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.