TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14465	43618;43619;43620	chr2:178632613;178632612;178632611	chr2:179497340;179497339;179497338
N2AB	12824	38695;38696;38697	chr2:178632613;178632612;178632611	chr2:179497340;179497339;179497338
N2A	11897	35914;35915;35916	chr2:178632613;178632612;178632611	chr2:179497340;179497339;179497338
N2B	5400	16423;16424;16425	chr2:178632613;178632612;178632611	chr2:179497340;179497339;179497338
Novex-1	5525	16798;16799;16800	chr2:178632613;178632612;178632611	chr2:179497340;179497339;179497338
Novex-2	5592	16999;17000;17001	chr2:178632613;178632612;178632611	chr2:179497340;179497339;179497338
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-95
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.1372
• 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/M	None	None	0.942	D	0.683	0.163	0.412328234245	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2279	likely_benign	0.234	benign	-2.164	Highly Destabilizing	0.822	D	0.563	neutral	D	0.579939606	None	None	N
V/C	0.7553	likely_pathogenic	0.7623	pathogenic	-1.583	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
V/D	0.4076	ambiguous	0.4152	ambiguous	-2.542	Highly Destabilizing	0.993	D	0.781	deleterious	None	None	None	None	N
V/E	0.3078	likely_benign	0.3219	benign	-2.396	Highly Destabilizing	0.99	D	0.715	prob.delet.	N	0.507134781	None	None	N
V/F	0.1403	likely_benign	0.1378	benign	-1.288	Destabilizing	0.956	D	0.735	prob.delet.	None	None	None	None	N
V/G	0.2865	likely_benign	0.2886	benign	-2.627	Highly Destabilizing	0.971	D	0.771	deleterious	D	0.622824138	None	None	N
V/H	0.5116	ambiguous	0.5124	ambiguous	-2.175	Highly Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
V/I	0.075	likely_benign	0.0763	benign	-0.898	Destabilizing	0.019	N	0.266	neutral	None	None	None	None	N
V/K	0.3152	likely_benign	0.3349	benign	-1.818	Destabilizing	0.978	D	0.72	prob.delet.	None	None	None	None	N
V/L	0.158	likely_benign	0.1661	benign	-0.898	Destabilizing	0.014	N	0.353	neutral	N	0.499914249	None	None	N
V/M	0.1432	likely_benign	0.1441	benign	-0.845	Destabilizing	0.942	D	0.683	prob.neutral	D	0.54055012	None	None	N
V/N	0.2932	likely_benign	0.2996	benign	-1.921	Destabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
V/P	0.9371	likely_pathogenic	0.9368	pathogenic	-1.292	Destabilizing	0.993	D	0.719	prob.delet.	None	None	None	None	N
V/Q	0.3381	likely_benign	0.3516	ambiguous	-1.899	Destabilizing	0.993	D	0.731	prob.delet.	None	None	None	None	N
V/R	0.2661	likely_benign	0.2756	benign	-1.428	Destabilizing	0.978	D	0.786	deleterious	None	None	None	None	N
V/S	0.2696	likely_benign	0.281	benign	-2.527	Highly Destabilizing	0.978	D	0.721	prob.delet.	None	None	None	None	N
V/T	0.2029	likely_benign	0.2126	benign	-2.262	Highly Destabilizing	0.86	D	0.615	neutral	None	None	None	None	N
V/W	0.7594	likely_pathogenic	0.7493	pathogenic	-1.705	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	N
V/Y	0.4597	ambiguous	0.4585	ambiguous	-1.409	Destabilizing	0.978	D	0.716	prob.delet.	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.