TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15927	48004;48005;48006	chr2:178617216;178617215;178617214	chr2:179481943;179481942;179481941
N2AB	14286	43081;43082;43083	chr2:178617216;178617215;178617214	chr2:179481943;179481942;179481941
N2A	13359	40300;40301;40302	chr2:178617216;178617215;178617214	chr2:179481943;179481942;179481941
N2B	6862	20809;20810;20811	chr2:178617216;178617215;178617214	chr2:179481943;179481942;179481941
Novex-1	6987	21184;21185;21186	chr2:178617216;178617215;178617214	chr2:179481943;179481942;179481941
Novex-2	7054	21385;21386;21387	chr2:178617216;178617215;178617214	chr2:179481943;179481942;179481941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-3
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.2282
• 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
G/V	rs2057501392	None	0.056	D	0.566	0.351	0.383089235449	gnomAD-4.0.0	7.14299E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.23613E-07	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
G/A	0.4071	ambiguous	0.4136	ambiguous	-0.512	Destabilizing	0.805	D	0.601	neutral	D	0.537801914	None	None	N
G/C	0.5033	ambiguous	0.4923	ambiguous	-0.79	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
G/D	0.2227	likely_benign	0.2284	benign	-1.076	Destabilizing	0.996	D	0.659	neutral	None	None	None	None	N
G/E	0.2972	likely_benign	0.3002	benign	-1.239	Destabilizing	0.983	D	0.713	prob.delet.	D	0.569627682	None	None	N
G/F	0.8577	likely_pathogenic	0.8536	pathogenic	-1.238	Destabilizing	0.154	N	0.639	neutral	None	None	None	None	N
G/H	0.6498	likely_pathogenic	0.6481	pathogenic	-0.832	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
G/I	0.785	likely_pathogenic	0.7914	pathogenic	-0.558	Destabilizing	0.95	D	0.696	prob.neutral	None	None	None	None	N
G/K	0.62	likely_pathogenic	0.6132	pathogenic	-1.043	Destabilizing	0.987	D	0.716	prob.delet.	None	None	None	None	N
G/L	0.7985	likely_pathogenic	0.8066	pathogenic	-0.558	Destabilizing	0.073	N	0.583	neutral	None	None	None	None	N
G/M	0.7958	likely_pathogenic	0.803	pathogenic	-0.335	Destabilizing	0.993	D	0.747	deleterious	None	None	None	None	N
G/N	0.311	likely_benign	0.3279	benign	-0.598	Destabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	N
G/P	0.9701	likely_pathogenic	0.9618	pathogenic	-0.508	Destabilizing	0.996	D	0.72	prob.delet.	None	None	None	None	N
G/Q	0.4917	ambiguous	0.5035	ambiguous	-0.955	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
G/R	0.5386	ambiguous	0.5242	ambiguous	-0.509	Destabilizing	0.983	D	0.719	prob.delet.	D	0.646917118	None	None	N
G/S	0.2297	likely_benign	0.2412	benign	-0.718	Destabilizing	0.987	D	0.666	neutral	None	None	None	None	N
G/T	0.4541	ambiguous	0.4691	ambiguous	-0.828	Destabilizing	0.975	D	0.683	prob.neutral	None	None	None	None	N
G/V	0.6379	likely_pathogenic	0.6474	pathogenic	-0.508	Destabilizing	0.056	N	0.566	neutral	D	0.648599914	None	None	N
G/W	0.6674	likely_pathogenic	0.6394	pathogenic	-1.398	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
G/Y	0.7031	likely_pathogenic	0.6939	pathogenic	-1.061	Destabilizing	0.95	D	0.742	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.