TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2889	8890;8891;8892	chr2:178769916;178769915;178769914	chr2:179634643;179634642;179634641
N2AB	2889	8890;8891;8892	chr2:178769916;178769915;178769914	chr2:179634643;179634642;179634641
N2A	2889	8890;8891;8892	chr2:178769916;178769915;178769914	chr2:179634643;179634642;179634641
N2B	2843	8752;8753;8754	chr2:178769916;178769915;178769914	chr2:179634643;179634642;179634641
Novex-1	2843	8752;8753;8754	chr2:178769916;178769915;178769914	chr2:179634643;179634642;179634641
Novex-2	2843	8752;8753;8754	chr2:178769916;178769915;178769914	chr2:179634643;179634642;179634641
Novex-3	2889	8890;8891;8892	chr2:178769916;178769915;178769914	chr2:179634643;179634642;179634641

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-19
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.3808
• 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/R	rs1245891851	0.134	0.142	N	0.26	0.162	0.320256813643	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.83E-06	0
K/R	rs1245891851	0.134	0.142	N	0.26	0.162	0.320256813643	gnomAD-4.0.0	1.36817E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7986E-06	0	0
K/T	None	None	0.988	N	0.646	0.522	0.555555669293	gnomAD-4.0.0	6.84087E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99302E-07	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	0.4661	ambiguous	0.5018	ambiguous	0.025	Stabilizing	0.968	D	0.567	neutral	None	None	None	None	N
K/C	0.7668	likely_pathogenic	0.8105	pathogenic	-0.352	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/D	0.6189	likely_pathogenic	0.6575	pathogenic	-0.186	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
K/E	0.1858	likely_benign	0.2191	benign	-0.183	Destabilizing	0.958	D	0.523	neutral	N	0.468159808	None	None	N
K/F	0.8971	likely_pathogenic	0.9084	pathogenic	-0.259	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/G	0.5199	ambiguous	0.5465	ambiguous	-0.133	Destabilizing	0.991	D	0.525	neutral	None	None	None	None	N
K/H	0.3666	ambiguous	0.3914	ambiguous	-0.268	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/I	0.6047	likely_pathogenic	0.6211	pathogenic	0.361	Stabilizing	0.994	D	0.684	prob.neutral	D	0.588878558	None	None	N
K/L	0.5439	ambiguous	0.5678	pathogenic	0.361	Stabilizing	0.991	D	0.525	neutral	None	None	None	None	N
K/M	0.3956	ambiguous	0.4405	ambiguous	-0.039	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/N	0.4116	ambiguous	0.4504	ambiguous	0.095	Stabilizing	0.988	D	0.659	neutral	D	0.557225818	None	None	N
K/P	0.8206	likely_pathogenic	0.8469	pathogenic	0.274	Stabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
K/Q	0.1321	likely_benign	0.1441	benign	-0.031	Destabilizing	0.988	D	0.65	neutral	N	0.461935819	None	None	N
K/R	0.0911	likely_benign	0.091	benign	-0.042	Destabilizing	0.142	N	0.26	neutral	N	0.495469927	None	None	N
K/S	0.4617	ambiguous	0.5019	ambiguous	-0.283	Destabilizing	0.968	D	0.582	neutral	None	None	None	None	N
K/T	0.2481	likely_benign	0.2798	benign	-0.15	Destabilizing	0.988	D	0.646	neutral	N	0.518920071	None	None	N
K/V	0.5322	ambiguous	0.5485	ambiguous	0.274	Stabilizing	0.995	D	0.643	neutral	None	None	None	None	N
K/W	0.8338	likely_pathogenic	0.8579	pathogenic	-0.353	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/Y	0.763	likely_pathogenic	0.7997	pathogenic	0.004	Stabilizing	0.998	D	0.653	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.