TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32911	98956;98957;98958	chr2:178539204;178539203;178539202	chr2:179403931;179403930;179403929
N2AB	31270	94033;94034;94035	chr2:178539204;178539203;178539202	chr2:179403931;179403930;179403929
N2A	30343	91252;91253;91254	chr2:178539204;178539203;178539202	chr2:179403931;179403930;179403929
N2B	23846	71761;71762;71763	chr2:178539204;178539203;178539202	chr2:179403931;179403930;179403929
Novex-1	23971	72136;72137;72138	chr2:178539204;178539203;178539202	chr2:179403931;179403930;179403929
Novex-2	24038	72337;72338;72339	chr2:178539204;178539203;178539202	chr2:179403931;179403930;179403929
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-128
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.4718
• 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
K/T	None	None	1.0	N	0.681	0.436	0.416581338634	gnomAD-4.0.0	1.59138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	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
K/A	0.6706	likely_pathogenic	0.7009	pathogenic	-0.178	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
K/C	0.9228	likely_pathogenic	0.921	pathogenic	-0.198	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.9398	likely_pathogenic	0.9411	pathogenic	-0.164	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/E	0.6492	likely_pathogenic	0.6849	pathogenic	-0.168	Destabilizing	0.999	D	0.562	neutral	N	0.483403436	None	None	N
K/F	0.9807	likely_pathogenic	0.9809	pathogenic	-0.583	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/G	0.7788	likely_pathogenic	0.8019	pathogenic	-0.381	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/H	0.6743	likely_pathogenic	0.6839	pathogenic	-0.927	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
K/I	0.8943	likely_pathogenic	0.8865	pathogenic	0.281	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/L	0.841	likely_pathogenic	0.8397	pathogenic	0.281	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
K/M	0.7501	likely_pathogenic	0.7637	pathogenic	0.478	Stabilizing	1.0	D	0.616	neutral	N	0.491714765	None	None	N
K/N	0.8475	likely_pathogenic	0.8646	pathogenic	0.184	Stabilizing	1.0	D	0.721	prob.delet.	N	0.511630187	None	None	N
K/P	0.906	likely_pathogenic	0.906	pathogenic	0.156	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/Q	0.3386	likely_benign	0.3457	ambiguous	-0.144	Destabilizing	1.0	D	0.716	prob.delet.	N	0.500471831	None	None	N
K/R	0.0982	likely_benign	0.0952	benign	0.004	Stabilizing	0.999	D	0.521	neutral	N	0.445253267	None	None	N
K/S	0.7432	likely_pathogenic	0.7702	pathogenic	-0.349	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/T	0.6782	likely_pathogenic	0.7071	pathogenic	-0.205	Destabilizing	1.0	D	0.681	prob.neutral	N	0.472543646	None	None	N
K/V	0.8205	likely_pathogenic	0.8077	pathogenic	0.156	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/W	0.9721	likely_pathogenic	0.9739	pathogenic	-0.526	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/Y	0.9377	likely_pathogenic	0.938	pathogenic	-0.123	Destabilizing	1.0	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.