TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9243	27952;27953;27954	chr2:178712103;178712102;178712101	chr2:179576830;179576829;179576828
N2AB	8926	27001;27002;27003	chr2:178712103;178712102;178712101	chr2:179576830;179576829;179576828
N2A	7999	24220;24221;24222	chr2:178712103;178712102;178712101	chr2:179576830;179576829;179576828
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-78
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.3557
• 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
T/P	None	None	0.979	D	0.374	0.354	0.487912462561	gnomAD-4.0.0	6.84215E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99475E-07	0	0
T/S	None	None	0.472	N	0.297	0.085	0.190952846119	gnomAD-4.0.0	6.84215E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99475E-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
T/A	0.1018	likely_benign	0.1372	benign	-0.544	Destabilizing	0.309	N	0.264	neutral	N	0.467679914	None	None	N
T/C	0.5968	likely_pathogenic	0.6662	pathogenic	-0.401	Destabilizing	0.996	D	0.392	neutral	None	None	None	None	N
T/D	0.5327	ambiguous	0.6625	pathogenic	0.493	Stabilizing	0.854	D	0.382	neutral	None	None	None	None	N
T/E	0.3613	ambiguous	0.4663	ambiguous	0.465	Stabilizing	0.742	D	0.335	neutral	None	None	None	None	N
T/F	0.3498	ambiguous	0.4569	ambiguous	-0.894	Destabilizing	0.91	D	0.423	neutral	None	None	None	None	N
T/G	0.3135	likely_benign	0.4026	ambiguous	-0.727	Destabilizing	0.004	N	0.219	neutral	None	None	None	None	N
T/H	0.3221	likely_benign	0.4221	ambiguous	-0.887	Destabilizing	0.984	D	0.411	neutral	None	None	None	None	N
T/I	0.2292	likely_benign	0.2967	benign	-0.17	Destabilizing	0.521	D	0.393	neutral	N	0.493405078	None	None	N
T/K	0.2108	likely_benign	0.3016	benign	-0.322	Destabilizing	0.521	D	0.339	neutral	N	0.449054081	None	None	N
T/L	0.1411	likely_benign	0.1964	benign	-0.17	Destabilizing	0.17	N	0.335	neutral	None	None	None	None	N
T/M	0.1004	likely_benign	0.1278	benign	-0.176	Destabilizing	0.206	N	0.283	neutral	None	None	None	None	N
T/N	0.169	likely_benign	0.2193	benign	-0.268	Destabilizing	0.854	D	0.266	neutral	None	None	None	None	N
T/P	0.5671	likely_pathogenic	0.7192	pathogenic	-0.265	Destabilizing	0.979	D	0.374	neutral	D	0.532366111	None	None	N
T/Q	0.2267	likely_benign	0.3075	benign	-0.372	Destabilizing	0.91	D	0.369	neutral	None	None	None	None	N
T/R	0.1575	likely_benign	0.2464	benign	-0.114	Destabilizing	0.003	N	0.233	neutral	N	0.462908813	None	None	N
T/S	0.1367	likely_benign	0.1717	benign	-0.556	Destabilizing	0.472	N	0.297	neutral	N	0.472968304	None	None	N
T/V	0.1717	likely_benign	0.2123	benign	-0.265	Destabilizing	0.59	D	0.241	neutral	None	None	None	None	N
T/W	0.6764	likely_pathogenic	0.7991	pathogenic	-0.895	Destabilizing	0.996	D	0.443	neutral	None	None	None	None	N
T/Y	0.3807	ambiguous	0.4954	ambiguous	-0.607	Destabilizing	0.953	D	0.421	neutral	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.