TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20828	62707;62708;62709	chr2:178589243;178589242;178589241	chr2:179453970;179453969;179453968
N2AB	19187	57784;57785;57786	chr2:178589243;178589242;178589241	chr2:179453970;179453969;179453968
N2A	18260	55003;55004;55005	chr2:178589243;178589242;178589241	chr2:179453970;179453969;179453968
N2B	11763	35512;35513;35514	chr2:178589243;178589242;178589241	chr2:179453970;179453969;179453968
Novex-1	11888	35887;35888;35889	chr2:178589243;178589242;178589241	chr2:179453970;179453969;179453968
Novex-2	11955	36088;36089;36090	chr2:178589243;178589242;178589241	chr2:179453970;179453969;179453968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-122
• Domain position: 60
• Structural Position: 137
• Q(SASA): 0.3597
• 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	rs2154183659	None	0.716	N	0.495	0.308	0.330331372229	gnomAD-4.0.0	3.18368E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85922E-06	0	3.02499E-05
K/T	None	None	0.946	N	0.681	0.328	0.306695030598	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	5.65803E-05	0	None	0	0	None	0	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
K/A	0.2067	likely_benign	0.217	benign	-0.591	Destabilizing	0.87	D	0.547	neutral	None	None	None	None	N
K/C	0.3775	ambiguous	0.3973	ambiguous	-0.923	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
K/D	0.6509	likely_pathogenic	0.6325	pathogenic	-0.842	Destabilizing	0.959	D	0.727	prob.delet.	None	None	None	None	N
K/E	0.2316	likely_benign	0.2126	benign	-0.753	Destabilizing	0.716	D	0.495	neutral	N	0.441802822	None	None	N
K/F	0.5411	ambiguous	0.5503	ambiguous	-0.603	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
K/G	0.4321	ambiguous	0.4259	ambiguous	-0.921	Destabilizing	0.959	D	0.671	neutral	None	None	None	None	N
K/H	0.1794	likely_benign	0.1897	benign	-1.352	Destabilizing	0.994	D	0.762	deleterious	None	None	None	None	N
K/I	0.155	likely_benign	0.1634	benign	0.251	Stabilizing	0.973	D	0.79	deleterious	N	0.442381612	None	None	N
K/L	0.2321	likely_benign	0.2422	benign	0.251	Stabilizing	0.959	D	0.671	neutral	None	None	None	None	N
K/M	0.1601	likely_benign	0.1626	benign	0.285	Stabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
K/N	0.3921	ambiguous	0.3998	ambiguous	-0.713	Destabilizing	0.946	D	0.635	neutral	N	0.467085268	None	None	N
K/P	0.9599	likely_pathogenic	0.9523	pathogenic	-0.001	Destabilizing	0.979	D	0.751	deleterious	None	None	None	None	N
K/Q	0.1026	likely_benign	0.1046	benign	-0.931	Destabilizing	0.946	D	0.619	neutral	N	0.472125729	None	None	N
K/R	0.074	likely_benign	0.0725	benign	-0.583	Destabilizing	0.035	N	0.38	neutral	N	0.461639376	None	None	N
K/S	0.2523	likely_benign	0.2618	benign	-1.298	Destabilizing	0.87	D	0.571	neutral	None	None	None	None	N
K/T	0.0858	likely_benign	0.0908	benign	-1.017	Destabilizing	0.946	D	0.681	prob.neutral	N	0.381596938	None	None	N
K/V	0.138	likely_benign	0.1428	benign	-0.001	Destabilizing	0.959	D	0.733	prob.delet.	None	None	None	None	N
K/W	0.6322	likely_pathogenic	0.6022	pathogenic	-0.514	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
K/Y	0.4449	ambiguous	0.4487	ambiguous	-0.114	Destabilizing	0.993	D	0.787	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.