TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9501	28726;28727;28728	chr2:178709818;178709817;178709816	chr2:179574545;179574544;179574543
N2AB	9184	27775;27776;27777	chr2:178709818;178709817;178709816	chr2:179574545;179574544;179574543
N2A	8257	24994;24995;24996	chr2:178709818;178709817;178709816	chr2:179574545;179574544;179574543
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-81
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6884
• 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
E/D	None	None	0.996	None	0.445	0.125	0.204665344411	gnomAD-4.0.0	6.84502E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99609E-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
E/A	0.3869	ambiguous	0.2889	benign	-0.019	Destabilizing	0.992	D	0.541	neutral	None	None	None	None	N
E/C	0.9803	likely_pathogenic	0.9643	pathogenic	0.299	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/D	0.1786	likely_benign	0.1165	benign	-0.088	Destabilizing	0.996	D	0.445	neutral	None	None	None	None	N
E/F	0.9599	likely_pathogenic	0.927	pathogenic	-0.177	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/G	0.3519	ambiguous	0.2545	benign	-0.126	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
E/H	0.8457	likely_pathogenic	0.7455	pathogenic	0.101	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
E/I	0.821	likely_pathogenic	0.7247	pathogenic	0.203	Stabilizing	0.998	D	0.704	prob.neutral	None	None	None	None	N
E/K	0.404	ambiguous	0.29	benign	0.737	Stabilizing	0.992	D	0.521	neutral	None	None	None	None	N
E/L	0.8098	likely_pathogenic	0.7186	pathogenic	0.203	Stabilizing	0.998	D	0.62	neutral	None	None	None	None	N
E/M	0.8365	likely_pathogenic	0.7564	pathogenic	0.261	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
E/N	0.5169	ambiguous	0.3672	ambiguous	0.56	Stabilizing	0.999	D	0.597	neutral	None	None	None	None	N
E/P	0.7721	likely_pathogenic	0.6318	pathogenic	0.147	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
E/Q	0.3637	ambiguous	0.2848	benign	0.57	Stabilizing	1.0	D	0.573	neutral	None	None	None	None	N
E/R	0.6232	likely_pathogenic	0.4992	ambiguous	0.705	Stabilizing	0.999	D	0.622	neutral	None	None	None	None	N
E/S	0.4428	ambiguous	0.3213	benign	0.446	Stabilizing	0.988	D	0.513	neutral	None	None	None	None	N
E/T	0.5412	ambiguous	0.419	ambiguous	0.544	Stabilizing	0.683	D	0.317	neutral	None	None	None	None	N
E/V	0.5974	likely_pathogenic	0.4858	ambiguous	0.147	Stabilizing	0.998	D	0.557	neutral	None	None	None	None	N
E/W	0.9876	likely_pathogenic	0.9732	pathogenic	-0.165	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/Y	0.9245	likely_pathogenic	0.8616	pathogenic	0.04	Stabilizing	1.0	D	0.675	prob.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.