TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21084	63475;63476;63477	chr2:178588157;178588156;178588155	chr2:179452884;179452883;179452882
N2AB	19443	58552;58553;58554	chr2:178588157;178588156;178588155	chr2:179452884;179452883;179452882
N2A	18516	55771;55772;55773	chr2:178588157;178588156;178588155	chr2:179452884;179452883;179452882
N2B	12019	36280;36281;36282	chr2:178588157;178588156;178588155	chr2:179452884;179452883;179452882
Novex-1	12144	36655;36656;36657	chr2:178588157;178588156;178588155	chr2:179452884;179452883;179452882
Novex-2	12211	36856;36857;36858	chr2:178588157;178588156;178588155	chr2:179452884;179452883;179452882
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-41
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1349
• 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/E	rs1342843033	-0.873	0.062	N	0.629	0.091	0.0806252709748	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.3E-05	None	0	0	0
G/E	rs1342843033	-0.873	0.062	N	0.629	0.091	0.0806252709748	gnomAD-4.0.0	1.60416E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44084E-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
G/A	0.0722	likely_benign	0.0918	benign	-0.309	Destabilizing	None	N	0.241	neutral	N	0.397883394	None	None	N
G/C	0.137	likely_benign	0.1551	benign	-0.547	Destabilizing	0.824	D	0.674	neutral	None	None	None	None	N
G/D	0.3697	ambiguous	0.4544	ambiguous	-2.007	Highly Destabilizing	0.149	N	0.65	neutral	None	None	None	None	N
G/E	0.2304	likely_benign	0.29	benign	-1.763	Destabilizing	0.062	N	0.629	neutral	N	0.414178211	None	None	N
G/F	0.4874	ambiguous	0.5626	ambiguous	-0.189	Destabilizing	0.555	D	0.689	prob.neutral	None	None	None	None	N
G/H	0.361	ambiguous	0.4362	ambiguous	-1.816	Destabilizing	0.698	D	0.624	neutral	None	None	None	None	N
G/I	0.2097	likely_benign	0.2772	benign	0.979	Stabilizing	0.38	N	0.704	prob.neutral	None	None	None	None	N
G/K	0.3967	ambiguous	0.5231	ambiguous	-0.582	Destabilizing	0.001	N	0.555	neutral	None	None	None	None	N
G/L	0.2595	likely_benign	0.3165	benign	0.979	Stabilizing	0.081	N	0.709	prob.delet.	None	None	None	None	N
G/M	0.3084	likely_benign	0.3858	ambiguous	0.464	Stabilizing	0.824	D	0.675	prob.neutral	None	None	None	None	N
G/N	0.2844	likely_benign	0.3486	ambiguous	-1.016	Destabilizing	0.081	N	0.607	neutral	None	None	None	None	N
G/P	0.9668	likely_pathogenic	0.978	pathogenic	0.594	Stabilizing	0.38	N	0.671	neutral	None	None	None	None	N
G/Q	0.2721	likely_benign	0.3323	benign	-0.678	Destabilizing	0.001	N	0.553	neutral	None	None	None	None	N
G/R	0.2943	likely_benign	0.3886	ambiguous	-1.049	Destabilizing	0.188	N	0.676	prob.neutral	N	0.41192734	None	None	N
G/S	0.0751	likely_benign	0.0861	benign	-1.278	Destabilizing	0.001	N	0.191	neutral	None	None	None	None	N
G/T	0.1017	likely_benign	0.132	benign	-0.907	Destabilizing	0.081	N	0.649	neutral	None	None	None	None	N
G/V	0.1587	likely_benign	0.2104	benign	0.594	Stabilizing	0.062	N	0.713	prob.delet.	N	0.411852769	None	None	N
G/W	0.4422	ambiguous	0.4932	ambiguous	-1.21	Destabilizing	0.915	D	0.662	neutral	N	0.508187237	None	None	N
G/Y	0.3942	ambiguous	0.4733	ambiguous	-0.471	Destabilizing	0.555	D	0.687	prob.neutral	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.