TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6783	20572;20573;20574	chr2:178725975;178725974;178725973	chr2:179590702;179590701;179590700
N2AB	6466	19621;19622;19623	chr2:178725975;178725974;178725973	chr2:179590702;179590701;179590700
N2A	5539	16840;16841;16842	chr2:178725975;178725974;178725973	chr2:179590702;179590701;179590700
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-52
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.7056
• 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
E/V	None	None	0.99	N	0.676	0.518	0.701518117412	gnomAD-4.0.0	1.37092E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.33187E-05	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	0.1886	likely_benign	0.1908	benign	-0.891	Destabilizing	0.959	D	0.601	neutral	N	0.494037349	None	None	I
E/C	0.8563	likely_pathogenic	0.8645	pathogenic	-0.402	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
E/D	0.2242	likely_benign	0.2032	benign	-1.135	Destabilizing	0.753	D	0.523	neutral	N	0.487872057	None	None	I
E/F	0.6659	likely_pathogenic	0.6532	pathogenic	-0.672	Destabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	I
E/G	0.2673	likely_benign	0.2686	benign	-1.238	Destabilizing	0.994	D	0.661	neutral	N	0.506256255	None	None	I
E/H	0.4036	ambiguous	0.3885	ambiguous	-1.021	Destabilizing	0.231	N	0.439	neutral	None	None	None	None	I
E/I	0.2607	likely_benign	0.2813	benign	0.047	Stabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	I
E/K	0.1247	likely_benign	0.1332	benign	-0.606	Destabilizing	0.956	D	0.571	neutral	N	0.521282326	None	None	I
E/L	0.3288	likely_benign	0.348	ambiguous	0.047	Stabilizing	0.99	D	0.675	prob.neutral	None	None	None	None	I
E/M	0.3851	ambiguous	0.4065	ambiguous	0.618	Stabilizing	0.997	D	0.689	prob.neutral	None	None	None	None	I
E/N	0.2951	likely_benign	0.2902	benign	-0.987	Destabilizing	0.978	D	0.643	neutral	None	None	None	None	I
E/P	0.8943	likely_pathogenic	0.8938	pathogenic	-0.244	Destabilizing	0.989	D	0.717	prob.delet.	None	None	None	None	I
E/Q	0.1116	likely_benign	0.1108	benign	-0.869	Destabilizing	0.739	D	0.384	neutral	N	0.499349615	None	None	I
E/R	0.2245	likely_benign	0.2325	benign	-0.471	Destabilizing	0.995	D	0.638	neutral	None	None	None	None	I
E/S	0.2217	likely_benign	0.2182	benign	-1.327	Destabilizing	0.969	D	0.578	neutral	None	None	None	None	I
E/T	0.1931	likely_benign	0.2035	benign	-1.036	Destabilizing	0.997	D	0.699	prob.neutral	None	None	None	None	I
E/V	0.167	likely_benign	0.1804	benign	-0.244	Destabilizing	0.99	D	0.676	prob.neutral	N	0.489633257	None	None	I
E/W	0.8954	likely_pathogenic	0.8908	pathogenic	-0.526	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
E/Y	0.6009	likely_pathogenic	0.5875	pathogenic	-0.44	Destabilizing	0.998	D	0.707	prob.neutral	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.