TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7066	21421;21422;21423	chr2:178724063;178724062;178724061	chr2:179588790;179588789;179588788
N2AB	6749	20470;20471;20472	chr2:178724063;178724062;178724061	chr2:179588790;179588789;179588788
N2A	5822	17689;17690;17691	chr2:178724063;178724062;178724061	chr2:179588790;179588789;179588788
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-55
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.4443
• 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	rs553548392	-0.625	0.032	N	0.346	0.105	None	gnomAD-2.1.1	2.39978E-04	None	None	None	None	N	None	0	1.87298E-03	None	0	0	None	0	None	0	0	1.41044E-04
K/R	rs553548392	-0.625	0.032	N	0.346	0.105	None	gnomAD-3.1.2	1.31432E-04	None	None	None	None	N	None	0	1.31027E-03	0	0	0	None	0	0	0	0	0
K/R	rs553548392	-0.625	0.032	N	0.346	0.105	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
K/R	rs553548392	-0.625	0.032	N	0.346	0.105	None	gnomAD-4.0.0	1.28142E-04	None	None	None	None	N	None	0	1.61093E-03	None	0	0	None	0	0	0	0	1.42215E-04

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	0.4626	ambiguous	0.5661	pathogenic	-0.681	Destabilizing	0.86	D	0.565	neutral	None	None	None	None	N
K/C	0.8245	likely_pathogenic	0.8739	pathogenic	-0.946	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/D	0.7431	likely_pathogenic	0.8723	pathogenic	-0.979	Destabilizing	0.978	D	0.691	prob.neutral	None	None	None	None	N
K/E	0.2096	likely_benign	0.2951	benign	-0.839	Destabilizing	0.822	D	0.5	neutral	N	0.51433771	None	None	N
K/F	0.823	likely_pathogenic	0.892	pathogenic	-0.297	Destabilizing	0.956	D	0.721	prob.delet.	None	None	None	None	N
K/G	0.671	likely_pathogenic	0.7941	pathogenic	-1.079	Destabilizing	0.956	D	0.674	neutral	None	None	None	None	N
K/H	0.3643	ambiguous	0.453	ambiguous	-1.468	Destabilizing	0.994	D	0.686	prob.neutral	None	None	None	None	N
K/I	0.3866	ambiguous	0.4653	ambiguous	0.372	Stabilizing	0.89	D	0.677	prob.neutral	D	0.53069403	None	None	N
K/L	0.4509	ambiguous	0.5462	ambiguous	0.372	Stabilizing	0.019	N	0.423	neutral	None	None	None	None	N
K/M	0.2743	likely_benign	0.3431	ambiguous	0.257	Stabilizing	0.956	D	0.701	prob.neutral	None	None	None	None	N
K/N	0.5932	likely_pathogenic	0.7375	pathogenic	-1.056	Destabilizing	0.942	D	0.565	neutral	N	0.497431163	None	None	N
K/P	0.926	likely_pathogenic	0.9688	pathogenic	0.05	Stabilizing	0.993	D	0.699	prob.neutral	None	None	None	None	N
K/Q	0.1565	likely_benign	0.1856	benign	-1.088	Destabilizing	0.942	D	0.585	neutral	D	0.531115317	None	None	N
K/R	0.0784	likely_benign	0.087	benign	-0.962	Destabilizing	0.032	N	0.346	neutral	N	0.461428732	None	None	N
K/S	0.5407	ambiguous	0.6579	pathogenic	-1.598	Destabilizing	0.86	D	0.522	neutral	None	None	None	None	N
K/T	0.2183	likely_benign	0.2774	benign	-1.25	Destabilizing	0.822	D	0.629	neutral	N	0.482628137	None	None	N
K/V	0.3512	ambiguous	0.4331	ambiguous	0.05	Stabilizing	0.754	D	0.655	neutral	None	None	None	None	N
K/W	0.8214	likely_pathogenic	0.8755	pathogenic	-0.267	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
K/Y	0.7025	likely_pathogenic	0.7908	pathogenic	0.083	Stabilizing	0.993	D	0.718	prob.delet.	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.