TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8443	25552;25553;25554	chr2:178717547;178717546;178717545	chr2:179582274;179582273;179582272
N2AB	8126	24601;24602;24603	chr2:178717547;178717546;178717545	chr2:179582274;179582273;179582272
N2A	7199	21820;21821;21822	chr2:178717547;178717546;178717545	chr2:179582274;179582273;179582272
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-69
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1572
• 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
S/A	rs753445241	-0.844	0.002	N	0.233	0.158	0.20549828249	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
S/A	rs753445241	-0.844	0.002	N	0.233	0.158	0.20549828249	gnomAD-4.0.0	6.86063E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16648E-05	0
S/T	None	None	0.034	N	0.257	0.184	0.21737058555	gnomAD-4.0.0	1.37213E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80278E-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
S/A	0.1825	likely_benign	0.1554	benign	-1.021	Destabilizing	0.002	N	0.233	neutral	N	0.516297793	None	None	N
S/C	0.1837	likely_benign	0.1402	benign	-0.646	Destabilizing	0.065	N	0.411	neutral	N	0.47102965	None	None	N
S/D	0.9527	likely_pathogenic	0.9512	pathogenic	-0.455	Destabilizing	0.983	D	0.737	prob.delet.	None	None	None	None	N
S/E	0.9758	likely_pathogenic	0.9767	pathogenic	-0.419	Destabilizing	0.976	D	0.737	prob.delet.	None	None	None	None	N
S/F	0.7847	likely_pathogenic	0.7552	pathogenic	-1.156	Destabilizing	0.998	D	0.794	deleterious	N	0.511193779	None	None	N
S/G	0.2834	likely_benign	0.252	benign	-1.298	Destabilizing	0.918	D	0.669	neutral	None	None	None	None	N
S/H	0.911	likely_pathogenic	0.9035	pathogenic	-1.665	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
S/I	0.7099	likely_pathogenic	0.6855	pathogenic	-0.372	Destabilizing	0.991	D	0.788	deleterious	None	None	None	None	N
S/K	0.9954	likely_pathogenic	0.9947	pathogenic	-0.611	Destabilizing	0.991	D	0.72	prob.delet.	None	None	None	None	N
S/L	0.4475	ambiguous	0.4426	ambiguous	-0.372	Destabilizing	0.991	D	0.709	prob.delet.	None	None	None	None	N
S/M	0.6608	likely_pathogenic	0.6662	pathogenic	-0.038	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
S/N	0.7133	likely_pathogenic	0.7088	pathogenic	-0.699	Destabilizing	0.875	D	0.733	prob.delet.	None	None	None	None	N
S/P	0.9845	likely_pathogenic	0.9809	pathogenic	-0.556	Destabilizing	0.994	D	0.796	deleterious	D	0.529551523	None	None	N
S/Q	0.9591	likely_pathogenic	0.9566	pathogenic	-0.835	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
S/R	0.9877	likely_pathogenic	0.9847	pathogenic	-0.538	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
S/T	0.1377	likely_benign	0.166	benign	-0.726	Destabilizing	0.034	N	0.257	neutral	N	0.512452199	None	None	N
S/V	0.5753	likely_pathogenic	0.5566	ambiguous	-0.556	Destabilizing	0.954	D	0.717	prob.delet.	None	None	None	None	N
S/W	0.9136	likely_pathogenic	0.9089	pathogenic	-1.089	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
S/Y	0.783	likely_pathogenic	0.761	pathogenic	-0.821	Destabilizing	0.999	D	0.79	deleterious	D	0.522968158	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.