TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31511	94756;94757;94758	chr2:178546897;178546896;178546895	chr2:179411624;179411623;179411622
N2AB	29870	89833;89834;89835	chr2:178546897;178546896;178546895	chr2:179411624;179411623;179411622
N2A	28943	87052;87053;87054	chr2:178546897;178546896;178546895	chr2:179411624;179411623;179411622
N2B	22446	67561;67562;67563	chr2:178546897;178546896;178546895	chr2:179411624;179411623;179411622
Novex-1	22571	67936;67937;67938	chr2:178546897;178546896;178546895	chr2:179411624;179411623;179411622
Novex-2	22638	68137;68138;68139	chr2:178546897;178546896;178546895	chr2:179411624;179411623;179411622
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: Fn3-118
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.1733
• 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
G/D	None	None	1.0	N	0.818	0.429	0.446010312102	gnomAD-4.0.0	1.66789E-06	None	None	None	None	N	None	0	0	None	0	2.80568E-05	None	0	0	0	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
G/A	0.367	ambiguous	0.3146	benign	-0.829	Destabilizing	1.0	D	0.657	neutral	N	0.483307748	None	None	N
G/C	0.5869	likely_pathogenic	0.4558	ambiguous	-1.152	Destabilizing	1.0	D	0.822	deleterious	D	0.526962224	None	None	N
G/D	0.7887	likely_pathogenic	0.716	pathogenic	-1.589	Destabilizing	1.0	D	0.818	deleterious	N	0.482257791	None	None	N
G/E	0.7334	likely_pathogenic	0.6326	pathogenic	-1.6	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/F	0.9341	likely_pathogenic	0.8981	pathogenic	-1.1	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/H	0.8758	likely_pathogenic	0.8072	pathogenic	-1.621	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
G/I	0.8531	likely_pathogenic	0.7621	pathogenic	-0.29	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/K	0.8724	likely_pathogenic	0.7979	pathogenic	-1.375	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
G/L	0.8312	likely_pathogenic	0.7435	pathogenic	-0.29	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
G/M	0.8756	likely_pathogenic	0.8126	pathogenic	-0.321	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
G/N	0.7632	likely_pathogenic	0.6873	pathogenic	-1.162	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
G/P	0.9753	likely_pathogenic	0.9548	pathogenic	-0.427	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
G/Q	0.7435	likely_pathogenic	0.6462	pathogenic	-1.283	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
G/R	0.7731	likely_pathogenic	0.6705	pathogenic	-1.16	Destabilizing	1.0	D	0.861	deleterious	N	0.465720017	None	None	N
G/S	0.217	likely_benign	0.1903	benign	-1.431	Destabilizing	1.0	D	0.729	prob.delet.	N	0.507069729	None	None	N
G/T	0.4836	ambiguous	0.4177	ambiguous	-1.355	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/V	0.7199	likely_pathogenic	0.6062	pathogenic	-0.427	Destabilizing	1.0	D	0.885	deleterious	N	0.487777973	None	None	N
G/W	0.9207	likely_pathogenic	0.8759	pathogenic	-1.554	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/Y	0.9147	likely_pathogenic	0.8658	pathogenic	-1.098	Destabilizing	1.0	D	0.865	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.