TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5363	16312;16313;16314	chr2:178733089;178733088;178733087	chr2:179597816;179597815;179597814
N2AB	5046	15361;15362;15363	chr2:178733089;178733088;178733087	chr2:179597816;179597815;179597814
N2A	4119	12580;12581;12582	chr2:178733089;178733088;178733087	chr2:179597816;179597815;179597814
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: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-37
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2191
• 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/S	rs1272893628	-2.48	1.0	N	0.826	0.485	0.750113076578	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.75E-05	0	0
L/S	rs1272893628	-2.48	1.0	N	0.826	0.485	0.750113076578	gnomAD-4.0.0	4.85164E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89423E-05	0	5.8214E-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	0.7353	likely_pathogenic	0.7503	pathogenic	-2.082	Highly Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
L/C	0.8574	likely_pathogenic	0.8779	pathogenic	-1.481	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
L/D	0.9963	likely_pathogenic	0.9972	pathogenic	-1.263	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
L/E	0.972	likely_pathogenic	0.9779	pathogenic	-1.173	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/F	0.6236	likely_pathogenic	0.6561	pathogenic	-1.356	Destabilizing	1.0	D	0.719	prob.delet.	N	0.45779939	None	None	N
L/G	0.9568	likely_pathogenic	0.9628	pathogenic	-2.508	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/H	0.9521	likely_pathogenic	0.9645	pathogenic	-1.695	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/I	0.1525	likely_benign	0.1588	benign	-0.931	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
L/K	0.9694	likely_pathogenic	0.9763	pathogenic	-1.291	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/M	0.2511	likely_benign	0.2704	benign	-0.847	Destabilizing	1.0	D	0.74	deleterious	N	0.470890442	None	None	N
L/N	0.9676	likely_pathogenic	0.9748	pathogenic	-1.214	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/P	0.7157	likely_pathogenic	0.717	pathogenic	-1.287	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/Q	0.8627	likely_pathogenic	0.8934	pathogenic	-1.281	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/R	0.9358	likely_pathogenic	0.9498	pathogenic	-0.856	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/S	0.9142	likely_pathogenic	0.9277	pathogenic	-2.028	Highly Destabilizing	1.0	D	0.826	deleterious	N	0.495248894	None	None	N
L/T	0.7994	likely_pathogenic	0.8196	pathogenic	-1.8	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/V	0.1474	likely_benign	0.1431	benign	-1.287	Destabilizing	0.999	D	0.525	neutral	N	0.475396666	None	None	N
L/W	0.9313	likely_pathogenic	0.9528	pathogenic	-1.452	Destabilizing	1.0	D	0.737	prob.delet.	D	0.522760898	None	None	N
L/Y	0.9624	likely_pathogenic	0.9715	pathogenic	-1.22	Destabilizing	1.0	D	0.811	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.