TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6153	18682;18683;18684	chr2:178729796;178729795;178729794	chr2:179594523;179594522;179594521
N2AB	5836	17731;17732;17733	chr2:178729796;178729795;178729794	chr2:179594523;179594522;179594521
N2A	4909	14950;14951;14952	chr2:178729796;178729795;178729794	chr2:179594523;179594522;179594521
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-45
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.2254
• 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
G/D	rs374460910	-0.924	0.896	N	0.472	0.342	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	9.95E-05	0	None	0	None	0	8.88E-06	0
G/D	rs374460910	-0.924	0.896	N	0.472	0.342	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/D	rs374460910	-0.924	0.896	N	0.472	0.342	None	gnomAD-4.0.0	1.11553E-05	None	None	None	None	I	None	0	1.66778E-05	None	3.37883E-05	0	None	0	0	1.18671E-05	0	3.20246E-05

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
G/A	0.0969	likely_benign	0.105	benign	-0.537	Destabilizing	0.78	D	0.434	neutral	N	0.45288382	None	None	I
G/C	0.1901	likely_benign	0.185	benign	-0.96	Destabilizing	0.999	D	0.66	neutral	D	0.532115395	None	None	I
G/D	0.1271	likely_benign	0.1249	benign	-0.259	Destabilizing	0.896	D	0.472	neutral	N	0.46427425	None	None	I
G/E	0.1174	likely_benign	0.1242	benign	-0.341	Destabilizing	0.851	D	0.487	neutral	None	None	None	None	I
G/F	0.3565	ambiguous	0.4063	ambiguous	-0.985	Destabilizing	0.996	D	0.647	neutral	None	None	None	None	I
G/H	0.1864	likely_benign	0.2022	benign	-0.984	Destabilizing	0.997	D	0.607	neutral	None	None	None	None	I
G/I	0.172	likely_benign	0.1825	benign	-0.284	Destabilizing	0.988	D	0.651	neutral	None	None	None	None	I
G/K	0.1817	likely_benign	0.1992	benign	-0.793	Destabilizing	0.132	N	0.288	neutral	None	None	None	None	I
G/L	0.25	likely_benign	0.2835	benign	-0.284	Destabilizing	0.976	D	0.551	neutral	None	None	None	None	I
G/M	0.2998	likely_benign	0.3309	benign	-0.363	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	I
G/N	0.1637	likely_benign	0.169	benign	-0.485	Destabilizing	0.919	D	0.449	neutral	None	None	None	None	I
G/P	0.5498	ambiguous	0.5748	pathogenic	-0.329	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	I
G/Q	0.156	likely_benign	0.1743	benign	-0.652	Destabilizing	0.507	D	0.353	neutral	None	None	None	None	I
G/R	0.1223	likely_benign	0.1343	benign	-0.564	Destabilizing	0.059	N	0.351	neutral	N	0.359357583	None	None	I
G/S	0.0824	likely_benign	0.0845	benign	-0.848	Destabilizing	0.896	D	0.422	neutral	N	0.409997047	None	None	I
G/T	0.1142	likely_benign	0.1196	benign	-0.828	Destabilizing	0.988	D	0.517	neutral	None	None	None	None	I
G/V	0.1323	likely_benign	0.142	benign	-0.329	Destabilizing	0.984	D	0.571	neutral	N	0.449190154	None	None	I
G/W	0.2559	likely_benign	0.2789	benign	-1.235	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
G/Y	0.2465	likely_benign	0.2665	benign	-0.816	Destabilizing	0.996	D	0.651	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.