TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1917	5974;5975;5976	chr2:178776115;178776114;178776113	chr2:179640842;179640841;179640840
N2AB	1917	5974;5975;5976	chr2:178776115;178776114;178776113	chr2:179640842;179640841;179640840
N2A	1917	5974;5975;5976	chr2:178776115;178776114;178776113	chr2:179640842;179640841;179640840
N2B	1871	5836;5837;5838	chr2:178776115;178776114;178776113	chr2:179640842;179640841;179640840
Novex-1	1871	5836;5837;5838	chr2:178776115;178776114;178776113	chr2:179640842;179640841;179640840
Novex-2	1871	5836;5837;5838	chr2:178776115;178776114;178776113	chr2:179640842;179640841;179640840
Novex-3	1917	5974;5975;5976	chr2:178776115;178776114;178776113	chr2:179640842;179640841;179640840

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-9
• Domain position: 77
• Structural Position: 162
• Q(SASA): 0.6394
• Predicted PPI site: I

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
P/T	None	None	1.0	N	0.616	0.552	0.49676076625	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
P/A	0.1225	likely_benign	0.1508	benign	-0.403	Destabilizing	1.0	D	0.564	neutral	N	0.489183726	None	None	I
P/C	0.8517	likely_pathogenic	0.8747	pathogenic	-0.673	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/D	0.7151	likely_pathogenic	0.7916	pathogenic	-0.523	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
P/E	0.4713	ambiguous	0.5483	ambiguous	-0.652	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
P/F	0.8181	likely_pathogenic	0.8614	pathogenic	-0.761	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
P/G	0.5597	ambiguous	0.6228	pathogenic	-0.49	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
P/H	0.4565	ambiguous	0.5491	ambiguous	-0.081	Destabilizing	1.0	D	0.695	prob.neutral	D	0.550828441	None	None	I
P/I	0.4044	ambiguous	0.4426	ambiguous	-0.327	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/K	0.6164	likely_pathogenic	0.7216	pathogenic	-0.468	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	I
P/L	0.2214	likely_benign	0.2639	benign	-0.327	Destabilizing	1.0	D	0.727	prob.delet.	N	0.508939269	None	None	I
P/M	0.4455	ambiguous	0.4981	ambiguous	-0.436	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
P/N	0.539	ambiguous	0.6056	pathogenic	-0.219	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
P/Q	0.2956	likely_benign	0.3707	ambiguous	-0.485	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
P/R	0.4862	ambiguous	0.6192	pathogenic	0.078	Stabilizing	1.0	D	0.709	prob.delet.	N	0.50184939	None	None	I
P/S	0.2331	likely_benign	0.2836	benign	-0.503	Destabilizing	1.0	D	0.614	neutral	N	0.453440208	None	None	I
P/T	0.1541	likely_benign	0.1879	benign	-0.54	Destabilizing	1.0	D	0.616	neutral	N	0.50795922	None	None	I
P/V	0.3131	likely_benign	0.3508	ambiguous	-0.32	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
P/W	0.9264	likely_pathogenic	0.9498	pathogenic	-0.83	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/Y	0.8051	likely_pathogenic	0.851	pathogenic	-0.54	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I

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.