TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25299	76120;76121;76122	chr2:178570237;178570236;178570235	chr2:179434964;179434963;179434962
N2AB	23658	71197;71198;71199	chr2:178570237;178570236;178570235	chr2:179434964;179434963;179434962
N2A	22731	68416;68417;68418	chr2:178570237;178570236;178570235	chr2:179434964;179434963;179434962
N2B	16234	48925;48926;48927	chr2:178570237;178570236;178570235	chr2:179434964;179434963;179434962
Novex-1	16359	49300;49301;49302	chr2:178570237;178570236;178570235	chr2:179434964;179434963;179434962
Novex-2	16426	49501;49502;49503	chr2:178570237;178570236;178570235	chr2:179434964;179434963;179434962
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: Fn3-71
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.3516
• 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/N	rs754354789	0.202	0.651	N	0.334	0.337	0.263140351381	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	0
K/N	rs754354789	0.202	0.651	N	0.334	0.337	0.263140351381	gnomAD-4.0.0	9.55222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.59796E-05	0
K/Q	None	None	0.651	N	0.455	0.133	0.209622950755	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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	0.2907	likely_benign	0.3495	ambiguous	-0.281	Destabilizing	0.032	N	0.277	neutral	None	None	None	None	N
K/C	0.4029	ambiguous	0.5123	ambiguous	-0.29	Destabilizing	0.995	D	0.504	neutral	None	None	None	None	N
K/D	0.6799	likely_pathogenic	0.7292	pathogenic	0.016	Stabilizing	0.946	D	0.366	neutral	None	None	None	None	N
K/E	0.178	likely_benign	0.1985	benign	0.073	Stabilizing	0.651	D	0.377	neutral	N	0.468415341	None	None	N
K/F	0.7327	likely_pathogenic	0.7906	pathogenic	-0.195	Destabilizing	0.982	D	0.537	neutral	None	None	None	None	N
K/G	0.4022	ambiguous	0.465	ambiguous	-0.589	Destabilizing	0.553	D	0.394	neutral	None	None	None	None	N
K/H	0.2921	likely_benign	0.3282	benign	-1.01	Destabilizing	0.946	D	0.256	neutral	None	None	None	None	N
K/I	0.2993	likely_benign	0.3352	benign	0.482	Stabilizing	0.946	D	0.636	neutral	None	None	None	None	N
K/L	0.3213	likely_benign	0.3839	ambiguous	0.482	Stabilizing	0.712	D	0.365	neutral	None	None	None	None	N
K/M	0.2187	likely_benign	0.2549	benign	0.409	Stabilizing	0.976	D	0.243	neutral	N	0.471769951	None	None	N
K/N	0.4898	ambiguous	0.5347	ambiguous	-0.08	Destabilizing	0.651	D	0.334	neutral	N	0.487165181	None	None	N
K/P	0.9427	likely_pathogenic	0.9564	pathogenic	0.259	Stabilizing	0.946	D	0.385	neutral	None	None	None	None	N
K/Q	0.1123	likely_benign	0.1227	benign	-0.241	Destabilizing	0.651	D	0.455	neutral	N	0.48371008	None	None	N
K/R	0.0699	likely_benign	0.071	benign	-0.39	Destabilizing	0.002	N	0.162	neutral	N	0.436281493	None	None	N
K/S	0.3846	ambiguous	0.4348	ambiguous	-0.678	Destabilizing	0.553	D	0.268	neutral	None	None	None	None	N
K/T	0.1665	likely_benign	0.1824	benign	-0.438	Destabilizing	0.651	D	0.299	neutral	N	0.470855426	None	None	N
K/V	0.2069	likely_benign	0.2392	benign	0.259	Stabilizing	0.712	D	0.409	neutral	None	None	None	None	N
K/W	0.7259	likely_pathogenic	0.7762	pathogenic	-0.102	Destabilizing	0.995	D	0.629	neutral	None	None	None	None	N
K/Y	0.6358	likely_pathogenic	0.6971	pathogenic	0.209	Stabilizing	0.982	D	0.477	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.