TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24673	74242;74243;74244	chr2:178572115;178572114;178572113	chr2:179436842;179436841;179436840
N2AB	23032	69319;69320;69321	chr2:178572115;178572114;178572113	chr2:179436842;179436841;179436840
N2A	22105	66538;66539;66540	chr2:178572115;178572114;178572113	chr2:179436842;179436841;179436840
N2B	15608	47047;47048;47049	chr2:178572115;178572114;178572113	chr2:179436842;179436841;179436840
Novex-1	15733	47422;47423;47424	chr2:178572115;178572114;178572113	chr2:179436842;179436841;179436840
Novex-2	15800	47623;47624;47625	chr2:178572115;178572114;178572113	chr2:179436842;179436841;179436840
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: Fn3-67
• Domain position: 58
• Structural Position: 90
• Q(SASA): 0.2426
• 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
E/K	rs745794676	0.434	0.994	N	0.532	0.348	0.31501682445	gnomAD-4.0.0	1.59302E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88772E-05	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
E/A	0.183	likely_benign	0.177	benign	-0.911	Destabilizing	0.988	D	0.541	neutral	N	0.504781573	None	None	N
E/C	0.8572	likely_pathogenic	0.8573	pathogenic	-0.458	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/D	0.1366	likely_benign	0.1278	benign	-0.838	Destabilizing	0.016	N	0.441	neutral	N	0.473788321	None	None	N
E/F	0.8119	likely_pathogenic	0.8081	pathogenic	-0.249	Destabilizing	0.997	D	0.779	deleterious	None	None	None	None	N
E/G	0.2416	likely_benign	0.2349	benign	-1.248	Destabilizing	0.996	D	0.651	neutral	N	0.475914688	None	None	N
E/H	0.4023	ambiguous	0.4057	ambiguous	-0.275	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
E/I	0.4874	ambiguous	0.4792	ambiguous	0.005	Stabilizing	0.988	D	0.753	deleterious	None	None	None	None	N
E/K	0.1612	likely_benign	0.1647	benign	-0.354	Destabilizing	0.994	D	0.532	neutral	N	0.502434701	None	None	N
E/L	0.5416	ambiguous	0.5346	ambiguous	0.005	Stabilizing	0.254	N	0.499	neutral	None	None	None	None	N
E/M	0.4941	ambiguous	0.4846	ambiguous	0.322	Stabilizing	0.991	D	0.746	deleterious	None	None	None	None	N
E/N	0.2324	likely_benign	0.2191	benign	-0.925	Destabilizing	0.987	D	0.606	neutral	None	None	None	None	N
E/P	0.9705	likely_pathogenic	0.9673	pathogenic	-0.28	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
E/Q	0.1396	likely_benign	0.1369	benign	-0.805	Destabilizing	0.997	D	0.609	neutral	N	0.50316542	None	None	N
E/R	0.2954	likely_benign	0.302	benign	0.019	Stabilizing	0.999	D	0.627	neutral	None	None	None	None	N
E/S	0.1763	likely_benign	0.1716	benign	-1.187	Destabilizing	0.982	D	0.533	neutral	None	None	None	None	N
E/T	0.1943	likely_benign	0.1908	benign	-0.901	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
E/V	0.2789	likely_benign	0.2709	benign	-0.28	Destabilizing	0.927	D	0.653	neutral	N	0.477484851	None	None	N
E/W	0.927	likely_pathogenic	0.9266	pathogenic	0.096	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/Y	0.6803	likely_pathogenic	0.6815	pathogenic	0.034	Stabilizing	1.0	D	0.769	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.