TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3142	9649;9650;9651	chr2:178767806;178767805;178767804	chr2:179632533;179632532;179632531
N2AB	3142	9649;9650;9651	chr2:178767806;178767805;178767804	chr2:179632533;179632532;179632531
N2A	3142	9649;9650;9651	chr2:178767806;178767805;178767804	chr2:179632533;179632532;179632531
N2B	3096	9511;9512;9513	chr2:178767806;178767805;178767804	chr2:179632533;179632532;179632531
Novex-1	3096	9511;9512;9513	chr2:178767806;178767805;178767804	chr2:179632533;179632532;179632531
Novex-2	3096	9511;9512;9513	chr2:178767806;178767805;178767804	chr2:179632533;179632532;179632531
Novex-3	3142	9649;9650;9651	chr2:178767806;178767805;178767804	chr2:179632533;179632532;179632531

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-21
• Domain position: 85
• Structural Position: 178
• Q(SASA): 0.1716
• 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
V/G	rs1165830952	-2.75	1.0	D	0.743	0.655	0.56380075071	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
V/G	rs1165830952	-2.75	1.0	D	0.743	0.655	0.56380075071	gnomAD-4.0.0	1.59051E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85654E-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
V/A	0.9403	likely_pathogenic	0.9513	pathogenic	-2.055	Highly Destabilizing	0.998	D	0.525	neutral	D	0.584108924	None	None	N
V/C	0.9888	likely_pathogenic	0.9908	pathogenic	-1.66	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
V/D	0.9993	likely_pathogenic	0.9995	pathogenic	-2.756	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
V/E	0.9961	likely_pathogenic	0.9973	pathogenic	-2.678	Highly Destabilizing	1.0	D	0.736	prob.delet.	D	0.58628127	None	None	N
V/F	0.9811	likely_pathogenic	0.9872	pathogenic	-1.379	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/G	0.9802	likely_pathogenic	0.9832	pathogenic	-2.438	Highly Destabilizing	1.0	D	0.743	deleterious	D	0.58628127	None	None	N
V/H	0.9992	likely_pathogenic	0.9995	pathogenic	-1.927	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/I	0.1957	likely_benign	0.2075	benign	-1.04	Destabilizing	0.767	D	0.301	neutral	N	0.410650758	None	None	N
V/K	0.9969	likely_pathogenic	0.9981	pathogenic	-1.723	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/L	0.8924	likely_pathogenic	0.9212	pathogenic	-1.04	Destabilizing	0.981	D	0.447	neutral	N	0.4669032	None	None	N
V/M	0.9171	likely_pathogenic	0.9593	pathogenic	-1.0	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/N	0.9972	likely_pathogenic	0.9982	pathogenic	-1.767	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
V/P	0.9955	likely_pathogenic	0.9953	pathogenic	-1.35	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/Q	0.9954	likely_pathogenic	0.9973	pathogenic	-1.875	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/R	0.992	likely_pathogenic	0.9946	pathogenic	-1.239	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
V/S	0.9789	likely_pathogenic	0.9843	pathogenic	-2.262	Highly Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
V/T	0.9052	likely_pathogenic	0.9242	pathogenic	-2.081	Highly Destabilizing	0.998	D	0.664	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.697	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/Y	0.9986	likely_pathogenic	0.999	pathogenic	-1.431	Destabilizing	1.0	D	0.785	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.