TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5817	17674;17675;17676	chr2:178731317;178731316;178731315	chr2:179596044;179596043;179596042
N2AB	5500	16723;16724;16725	chr2:178731317;178731316;178731315	chr2:179596044;179596043;179596042
N2A	4573	13942;13943;13944	chr2:178731317;178731316;178731315	chr2:179596044;179596043;179596042
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-41
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.086
• 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
L/F	None	None	0.999	N	0.839	0.456	0.578326236229	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
L/I	None	None	0.992	N	0.623	0.363	0.467839254973	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
L/A	0.9554	likely_pathogenic	0.9663	pathogenic	-2.729	Highly Destabilizing	0.997	D	0.732	prob.delet.	None	None	None	None	N
L/C	0.9267	likely_pathogenic	0.9462	pathogenic	-2.5	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9994	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
L/E	0.9954	likely_pathogenic	0.9957	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/F	0.5983	likely_pathogenic	0.6556	pathogenic	-1.745	Destabilizing	0.999	D	0.839	deleterious	N	0.509603027	None	None	N
L/G	0.9921	likely_pathogenic	0.9935	pathogenic	-3.312	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
L/H	0.9787	likely_pathogenic	0.9833	pathogenic	-2.708	Highly Destabilizing	1.0	D	0.921	deleterious	D	0.528810146	None	None	N
L/I	0.2536	likely_benign	0.2795	benign	-1.014	Destabilizing	0.992	D	0.623	neutral	N	0.501534724	None	None	N
L/K	0.9925	likely_pathogenic	0.993	pathogenic	-1.933	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/M	0.4635	ambiguous	0.5031	ambiguous	-1.302	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/N	0.9948	likely_pathogenic	0.9958	pathogenic	-2.353	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/P	0.9953	likely_pathogenic	0.9955	pathogenic	-1.571	Destabilizing	1.0	D	0.923	deleterious	D	0.528810146	None	None	N
L/Q	0.9759	likely_pathogenic	0.9779	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
L/R	0.9786	likely_pathogenic	0.9801	pathogenic	-1.84	Destabilizing	1.0	D	0.935	deleterious	D	0.528810146	None	None	N
L/S	0.992	likely_pathogenic	0.9938	pathogenic	-3.227	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
L/T	0.9743	likely_pathogenic	0.9803	pathogenic	-2.78	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
L/V	0.2971	likely_benign	0.3453	ambiguous	-1.571	Destabilizing	0.767	D	0.355	neutral	N	0.515924073	None	None	N
L/W	0.9485	likely_pathogenic	0.9601	pathogenic	-1.924	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/Y	0.9528	likely_pathogenic	0.9643	pathogenic	-1.723	Destabilizing	1.0	D	0.884	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.