TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3047	9364;9365;9366	chr2:178768697;178768696;178768695	chr2:179633424;179633423;179633422
N2AB	3047	9364;9365;9366	chr2:178768697;178768696;178768695	chr2:179633424;179633423;179633422
N2A	3047	9364;9365;9366	chr2:178768697;178768696;178768695	chr2:179633424;179633423;179633422
N2B	3001	9226;9227;9228	chr2:178768697;178768696;178768695	chr2:179633424;179633423;179633422
Novex-1	3001	9226;9227;9228	chr2:178768697;178768696;178768695	chr2:179633424;179633423;179633422
Novex-2	3001	9226;9227;9228	chr2:178768697;178768696;178768695	chr2:179633424;179633423;179633422
Novex-3	3047	9364;9365;9366	chr2:178768697;178768696;178768695	chr2:179633424;179633423;179633422

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-20
• Domain position: 79
• Structural Position: 169
• Q(SASA): 0.1101
• 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/T	rs946142615	-0.406	0.044	N	0.341	0.188	0.183819452728	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
S/T	rs946142615	-0.406	0.044	N	0.341	0.188	0.183819452728	gnomAD-4.0.0	8.20963E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07917E-05	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	0.3233	likely_benign	0.2718	benign	-0.755	Destabilizing	0.91	D	0.575	neutral	N	0.482723168	None	None	N
S/C	0.4827	ambiguous	0.4173	ambiguous	-0.511	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
S/D	0.9876	likely_pathogenic	0.9861	pathogenic	-0.407	Destabilizing	0.985	D	0.725	prob.delet.	None	None	None	None	N
S/E	0.9934	likely_pathogenic	0.9922	pathogenic	-0.33	Destabilizing	0.985	D	0.721	prob.delet.	None	None	None	None	N
S/F	0.9842	likely_pathogenic	0.9802	pathogenic	-0.762	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
S/G	0.6027	likely_pathogenic	0.5063	ambiguous	-1.089	Destabilizing	0.985	D	0.715	prob.delet.	None	None	None	None	N
S/H	0.9776	likely_pathogenic	0.9765	pathogenic	-1.515	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
S/I	0.9654	likely_pathogenic	0.9552	pathogenic	0.047	Stabilizing	0.991	D	0.834	deleterious	None	None	None	None	N
S/K	0.9987	likely_pathogenic	0.9985	pathogenic	-0.543	Destabilizing	0.97	D	0.726	prob.delet.	None	None	None	None	N
S/L	0.8842	likely_pathogenic	0.8553	pathogenic	0.047	Stabilizing	0.961	D	0.814	deleterious	D	0.535078554	None	None	N
S/M	0.9013	likely_pathogenic	0.8799	pathogenic	0.183	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
S/N	0.9137	likely_pathogenic	0.8959	pathogenic	-0.77	Destabilizing	0.985	D	0.725	prob.delet.	None	None	None	None	N
S/P	0.9972	likely_pathogenic	0.9972	pathogenic	-0.184	Destabilizing	0.998	D	0.813	deleterious	D	0.535257814	None	None	N
S/Q	0.9881	likely_pathogenic	0.9852	pathogenic	-0.738	Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
S/R	0.9974	likely_pathogenic	0.9966	pathogenic	-0.65	Destabilizing	0.996	D	0.806	deleterious	None	None	None	None	N
S/T	0.1918	likely_benign	0.1783	benign	-0.679	Destabilizing	0.044	N	0.341	neutral	N	0.44450039	None	None	N
S/V	0.8911	likely_pathogenic	0.8662	pathogenic	-0.184	Destabilizing	0.97	D	0.816	deleterious	None	None	None	None	N
S/W	0.9912	likely_pathogenic	0.9898	pathogenic	-0.812	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
S/Y	0.9694	likely_pathogenic	0.9665	pathogenic	-0.484	Destabilizing	0.999	D	0.853	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.