TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13957	42094;42095;42096	chr2:178635455;178635454;178635453	chr2:179500182;179500181;179500180
N2AB	12316	37171;37172;37173	chr2:178635455;178635454;178635453	chr2:179500182;179500181;179500180
N2A	11389	34390;34391;34392	chr2:178635455;178635454;178635453	chr2:179500182;179500181;179500180
N2B	4892	14899;14900;14901	chr2:178635455;178635454;178635453	chr2:179500182;179500181;179500180
Novex-1	5017	15274;15275;15276	chr2:178635455;178635454;178635453	chr2:179500182;179500181;179500180
Novex-2	5084	15475;15476;15477	chr2:178635455;178635454;178635453	chr2:179500182;179500181;179500180
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: Ig-89
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.6868
• 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	None	None	0.007	D	0.247	0.202	0.222439326576	gnomAD-4.0.0	6.87104E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01808E-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	0.6446	likely_pathogenic	0.6262	pathogenic	-0.565	Destabilizing	0.74	D	0.575	neutral	None	None	None	None	N
K/C	0.8896	likely_pathogenic	0.8647	pathogenic	-0.583	Destabilizing	0.996	D	0.645	neutral	None	None	None	None	N
K/D	0.8748	likely_pathogenic	0.8697	pathogenic	-0.198	Destabilizing	0.587	D	0.661	prob.neutral	None	None	None	None	N
K/E	0.5406	ambiguous	0.4918	ambiguous	-0.083	Destabilizing	0.682	D	0.53	neutral	D	0.58236	None	None	N
K/F	0.8945	likely_pathogenic	0.8773	pathogenic	-0.186	Destabilizing	0.996	D	0.636	neutral	None	None	None	None	N
K/G	0.8167	likely_pathogenic	0.8107	pathogenic	-0.943	Destabilizing	0.587	D	0.536	neutral	None	None	None	None	N
K/H	0.448	ambiguous	0.4054	ambiguous	-1.272	Destabilizing	0.909	D	0.63	neutral	None	None	None	None	N
K/I	0.5414	ambiguous	0.5048	ambiguous	0.417	Stabilizing	0.953	D	0.686	prob.delet.	None	None	None	None	N
K/L	0.5603	ambiguous	0.5385	ambiguous	0.417	Stabilizing	0.953	D	0.574	neutral	None	None	None	None	N
K/M	0.4364	ambiguous	0.4001	ambiguous	0.249	Stabilizing	0.994	D	0.643	neutral	D	0.626149181	None	None	N
K/N	0.5846	likely_pathogenic	0.6104	pathogenic	-0.535	Destabilizing	0.007	N	0.247	neutral	D	0.624027255	None	None	N
K/P	0.9376	likely_pathogenic	0.9482	pathogenic	0.12	Stabilizing	0.953	D	0.683	prob.neutral	None	None	None	None	N
K/Q	0.2859	likely_benign	0.2507	benign	-0.583	Destabilizing	0.883	D	0.634	neutral	D	0.582500837	None	None	N
K/R	0.115	likely_benign	0.1122	benign	-0.683	Destabilizing	0.682	D	0.567	neutral	N	0.52070235	None	None	N
K/S	0.6714	likely_pathogenic	0.658	pathogenic	-1.165	Destabilizing	0.587	D	0.519	neutral	None	None	None	None	N
K/T	0.3413	ambiguous	0.2993	benign	-0.843	Destabilizing	0.682	D	0.655	prob.neutral	D	0.624027255	None	None	N
K/V	0.4571	ambiguous	0.4395	ambiguous	0.12	Stabilizing	0.953	D	0.681	prob.neutral	None	None	None	None	N
K/W	0.9277	likely_pathogenic	0.9133	pathogenic	-0.074	Destabilizing	0.996	D	0.583	neutral	None	None	None	None	N
K/Y	0.7942	likely_pathogenic	0.7879	pathogenic	0.205	Stabilizing	0.984	D	0.665	prob.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.