TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27521	82786;82787;82788	chr2:178563571;178563570;178563569	chr2:179428298;179428297;179428296
N2AB	25880	77863;77864;77865	chr2:178563571;178563570;178563569	chr2:179428298;179428297;179428296
N2A	24953	75082;75083;75084	chr2:178563571;178563570;178563569	chr2:179428298;179428297;179428296
N2B	18456	55591;55592;55593	chr2:178563571;178563570;178563569	chr2:179428298;179428297;179428296
Novex-1	18581	55966;55967;55968	chr2:178563571;178563570;178563569	chr2:179428298;179428297;179428296
Novex-2	18648	56167;56168;56169	chr2:178563571;178563570;178563569	chr2:179428298;179428297;179428296
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: Fn3-88
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.7196
• 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/E	rs1060500417	0.064	0.999	N	0.644	0.277	0.332133492242	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/E	rs1060500417	0.064	0.999	N	0.644	0.277	0.332133492242	gnomAD-4.0.0	3.18249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71677E-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	0.8965	likely_pathogenic	0.8881	pathogenic	0.069	Stabilizing	0.999	D	0.63	neutral	None	None	None	None	N
K/C	0.9381	likely_pathogenic	0.9387	pathogenic	-0.305	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/D	0.9644	likely_pathogenic	0.96	pathogenic	-0.196	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/E	0.8486	likely_pathogenic	0.8433	pathogenic	-0.208	Destabilizing	0.999	D	0.644	neutral	N	0.484347585	None	None	N
K/F	0.9829	likely_pathogenic	0.9822	pathogenic	-0.256	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/G	0.8322	likely_pathogenic	0.8233	pathogenic	-0.067	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/H	0.6786	likely_pathogenic	0.6869	pathogenic	-0.198	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/I	0.9197	likely_pathogenic	0.9102	pathogenic	0.343	Stabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
K/L	0.8724	likely_pathogenic	0.8648	pathogenic	0.343	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/M	0.8444	likely_pathogenic	0.8304	pathogenic	-0.014	Destabilizing	1.0	D	0.667	neutral	N	0.475065314	None	None	N
K/N	0.9447	likely_pathogenic	0.9362	pathogenic	0.174	Stabilizing	1.0	D	0.752	deleterious	N	0.466302675	None	None	N
K/P	0.9163	likely_pathogenic	0.9119	pathogenic	0.275	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	N
K/Q	0.4689	ambiguous	0.4696	ambiguous	0.024	Stabilizing	1.0	D	0.749	deleterious	N	0.470038885	None	None	N
K/R	0.075	likely_benign	0.0769	benign	-0.022	Destabilizing	0.999	D	0.608	neutral	N	0.481480639	None	None	N
K/S	0.9136	likely_pathogenic	0.9004	pathogenic	-0.197	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/T	0.7934	likely_pathogenic	0.7782	pathogenic	-0.091	Destabilizing	1.0	D	0.672	neutral	N	0.472322438	None	None	N
K/V	0.8885	likely_pathogenic	0.8779	pathogenic	0.275	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/W	0.9268	likely_pathogenic	0.9317	pathogenic	-0.357	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.9283	likely_pathogenic	0.9217	pathogenic	-0.001	Destabilizing	1.0	D	0.646	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.