TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7508	22747;22748;22749	chr2:178722265;178722264;178722263	chr2:179586992;179586991;179586990
N2AB	7191	21796;21797;21798	chr2:178722265;178722264;178722263	chr2:179586992;179586991;179586990
N2A	6264	19015;19016;19017	chr2:178722265;178722264;178722263	chr2:179586992;179586991;179586990
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-59
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.6864
• 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/S	rs1241417806	None	0.055	N	0.233	0.19	0.230578612272	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	1.92753E-04	None	0	0	0	0	0
A/S	rs1241417806	None	0.055	N	0.233	0.19	0.230578612272	gnomAD-4.0.0	2.68796E-06	None	None	None	None	I	None	0	0	None	0	2.44439E-05	None	0	0	2.49415E-06	0	0
A/T	rs1241417806	-0.625	0.012	N	0.206	0.2	0.233785782151	gnomAD-2.1.1	4.56E-06	None	None	None	None	I	None	0	0	None	0	5.87E-05	None	0	None	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	0.5523	ambiguous	0.5518	ambiguous	-1.159	Destabilizing	0.356	N	0.359	neutral	None	None	None	None	I
A/D	0.8106	likely_pathogenic	0.8595	pathogenic	-1.47	Destabilizing	0.356	N	0.363	neutral	None	None	None	None	I
A/E	0.7047	likely_pathogenic	0.7663	pathogenic	-1.523	Destabilizing	0.106	N	0.332	neutral	N	0.456183202	None	None	I
A/F	0.5061	ambiguous	0.5454	ambiguous	-1.207	Destabilizing	0.214	N	0.357	neutral	None	None	None	None	I
A/G	0.2365	likely_benign	0.2706	benign	-1.178	Destabilizing	0.106	N	0.207	neutral	N	0.456183202	None	None	I
A/H	0.862	likely_pathogenic	0.8905	pathogenic	-1.209	Destabilizing	0.864	D	0.334	neutral	None	None	None	None	I
A/I	0.1763	likely_benign	0.1834	benign	-0.559	Destabilizing	None	N	0.142	neutral	None	None	None	None	I
A/K	0.888	likely_pathogenic	0.9206	pathogenic	-1.083	Destabilizing	0.136	N	0.335	neutral	None	None	None	None	I
A/L	0.1412	likely_benign	0.1515	benign	-0.559	Destabilizing	None	N	0.116	neutral	None	None	None	None	I
A/M	0.2796	likely_benign	0.3056	benign	-0.544	Destabilizing	0.214	N	0.375	neutral	None	None	None	None	I
A/N	0.649	likely_pathogenic	0.696	pathogenic	-0.872	Destabilizing	0.628	D	0.363	neutral	None	None	None	None	I
A/P	0.3256	likely_benign	0.3687	ambiguous	-0.658	Destabilizing	0.295	N	0.386	neutral	N	0.45635656	None	None	I
A/Q	0.742	likely_pathogenic	0.798	pathogenic	-1.125	Destabilizing	0.628	D	0.375	neutral	None	None	None	None	I
A/R	0.8206	likely_pathogenic	0.8673	pathogenic	-0.713	Destabilizing	0.356	N	0.385	neutral	None	None	None	None	I
A/S	0.1587	likely_benign	0.1708	benign	-1.192	Destabilizing	0.055	N	0.233	neutral	N	0.456183202	None	None	I
A/T	0.1068	likely_benign	0.1088	benign	-1.164	Destabilizing	0.012	N	0.206	neutral	N	0.437424083	None	None	I
A/V	0.0887	likely_benign	0.0907	benign	-0.658	Destabilizing	None	N	0.077	neutral	N	0.286355761	None	None	I
A/W	0.8962	likely_pathogenic	0.9265	pathogenic	-1.442	Destabilizing	0.864	D	0.377	neutral	None	None	None	None	I
A/Y	0.7619	likely_pathogenic	0.8058	pathogenic	-1.06	Destabilizing	0.356	N	0.382	neutral	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.