TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19799	59620;59621;59622	chr2:178592610;178592609;178592608	chr2:179457337;179457336;179457335
N2AB	18158	54697;54698;54699	chr2:178592610;178592609;178592608	chr2:179457337;179457336;179457335
N2A	17231	51916;51917;51918	chr2:178592610;178592609;178592608	chr2:179457337;179457336;179457335
N2B	10734	32425;32426;32427	chr2:178592610;178592609;178592608	chr2:179457337;179457336;179457335
Novex-1	10859	32800;32801;32802	chr2:178592610;178592609;178592608	chr2:179457337;179457336;179457335
Novex-2	10926	33001;33002;33003	chr2:178592610;178592609;178592608	chr2:179457337;179457336;179457335
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-119
• Domain position: 10
• Structural Position: 18
• Q(SASA): 0.7845
• 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
K/N	rs570087924	0.066	0.117	N	0.37	0.126	0.192905019026	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
K/N	rs570087924	0.066	0.117	N	0.37	0.126	0.192905019026	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93798E-04	None	0	0	0	0	0
K/N	rs570087924	0.066	0.117	N	0.37	0.126	0.192905019026	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
K/N	rs570087924	0.066	0.117	N	0.37	0.126	0.192905019026	gnomAD-4.0.0	6.56935E-06	None	None	None	None	N	None	0	0	None	0	1.9425E-04	None	0	0	0	0	0
K/R	None	None	None	N	0.233	0.111	0.119812018005	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85945E-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
K/A	0.5821	likely_pathogenic	0.4515	ambiguous	-0.111	Destabilizing	0.035	N	0.414	neutral	None	None	None	None	N
K/C	0.7746	likely_pathogenic	0.6664	pathogenic	-0.391	Destabilizing	0.935	D	0.444	neutral	None	None	None	None	N
K/D	0.8985	likely_pathogenic	0.8448	pathogenic	0.202	Stabilizing	0.38	N	0.416	neutral	None	None	None	None	N
K/E	0.4752	ambiguous	0.3726	ambiguous	0.248	Stabilizing	0.062	N	0.331	neutral	N	0.513164275	None	None	N
K/F	0.8434	likely_pathogenic	0.7431	pathogenic	-0.126	Destabilizing	0.38	N	0.456	neutral	None	None	None	None	N
K/G	0.7228	likely_pathogenic	0.5995	pathogenic	-0.361	Destabilizing	0.149	N	0.471	neutral	None	None	None	None	N
K/H	0.3978	ambiguous	0.3031	benign	-0.528	Destabilizing	0.555	D	0.419	neutral	None	None	None	None	N
K/I	0.5546	ambiguous	0.4183	ambiguous	0.482	Stabilizing	0.062	N	0.463	neutral	N	0.518687524	None	None	N
K/L	0.4182	ambiguous	0.2986	benign	0.482	Stabilizing	0.001	N	0.286	neutral	None	None	None	None	N
K/M	0.2729	likely_benign	0.2009	benign	0.129	Stabilizing	0.002	N	0.299	neutral	None	None	None	None	N
K/N	0.7337	likely_pathogenic	0.626	pathogenic	-0.022	Destabilizing	0.117	N	0.37	neutral	N	0.51368435	None	None	N
K/P	0.7698	likely_pathogenic	0.6775	pathogenic	0.314	Stabilizing	0.555	D	0.429	neutral	None	None	None	None	N
K/Q	0.196	likely_benign	0.1449	benign	-0.117	Destabilizing	0.062	N	0.38	neutral	N	0.50769974	None	None	N
K/R	0.0778	likely_benign	0.0687	benign	-0.147	Destabilizing	None	N	0.233	neutral	N	0.459831222	None	None	N
K/S	0.7069	likely_pathogenic	0.5921	pathogenic	-0.563	Destabilizing	0.149	N	0.34	neutral	None	None	None	None	N
K/T	0.3659	ambiguous	0.2829	benign	-0.348	Destabilizing	0.117	N	0.416	neutral	N	0.50435279	None	None	N
K/V	0.4747	ambiguous	0.3503	ambiguous	0.314	Stabilizing	0.081	N	0.427	neutral	None	None	None	None	N
K/W	0.8231	likely_pathogenic	0.7027	pathogenic	-0.112	Destabilizing	0.935	D	0.451	neutral	None	None	None	None	N
K/Y	0.7718	likely_pathogenic	0.661	pathogenic	0.215	Stabilizing	0.555	D	0.467	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.