TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24848	74767;74768;74769	chr2:178571590;178571589;178571588	chr2:179436317;179436316;179436315
N2AB	23207	69844;69845;69846	chr2:178571590;178571589;178571588	chr2:179436317;179436316;179436315
N2A	22280	67063;67064;67065	chr2:178571590;178571589;178571588	chr2:179436317;179436316;179436315
N2B	15783	47572;47573;47574	chr2:178571590;178571589;178571588	chr2:179436317;179436316;179436315
Novex-1	15908	47947;47948;47949	chr2:178571590;178571589;178571588	chr2:179436317;179436316;179436315
Novex-2	15975	48148;48149;48150	chr2:178571590;178571589;178571588	chr2:179436317;179436316;179436315
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: Fn3-68
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.1627
• 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/Q	None	None	0.993	N	0.809	0.332	0.297375071883	gnomAD-4.0.0	1.59248E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-05	0
K/T	None	None	0.997	N	0.777	0.394	0.367042808489	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9159	likely_pathogenic	0.9253	pathogenic	-1.435	Destabilizing	0.983	D	0.669	neutral	None	None	None	None	N
K/C	0.8075	likely_pathogenic	0.8208	pathogenic	-1.458	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/D	0.9964	likely_pathogenic	0.9966	pathogenic	-2.19	Highly Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
K/E	0.8708	likely_pathogenic	0.8881	pathogenic	-1.859	Destabilizing	0.977	D	0.664	neutral	N	0.510882204	None	None	N
K/F	0.9498	likely_pathogenic	0.9492	pathogenic	-0.629	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/G	0.9629	likely_pathogenic	0.9651	pathogenic	-1.935	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
K/H	0.7526	likely_pathogenic	0.7637	pathogenic	-1.634	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
K/I	0.7101	likely_pathogenic	0.7496	pathogenic	0.004	Stabilizing	0.997	D	0.841	deleterious	N	0.471493689	None	None	N
K/L	0.6954	likely_pathogenic	0.715	pathogenic	0.004	Stabilizing	0.995	D	0.748	deleterious	None	None	None	None	N
K/M	0.3631	ambiguous	0.3823	ambiguous	-0.39	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/N	0.9738	likely_pathogenic	0.9765	pathogenic	-2.0	Highly Destabilizing	0.993	D	0.809	deleterious	N	0.517630154	None	None	N
K/P	0.9993	likely_pathogenic	0.9993	pathogenic	-0.458	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
K/Q	0.3588	ambiguous	0.3929	ambiguous	-1.574	Destabilizing	0.993	D	0.809	deleterious	N	0.478788297	None	None	N
K/R	0.1339	likely_benign	0.1451	benign	-0.919	Destabilizing	0.235	N	0.397	neutral	N	0.51026475	None	None	N
K/S	0.948	likely_pathogenic	0.9556	pathogenic	-2.481	Highly Destabilizing	0.983	D	0.693	prob.neutral	None	None	None	None	N
K/T	0.8156	likely_pathogenic	0.8421	pathogenic	-1.882	Destabilizing	0.997	D	0.777	deleterious	N	0.493485511	None	None	N
K/V	0.7072	likely_pathogenic	0.7289	pathogenic	-0.458	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
K/W	0.9266	likely_pathogenic	0.9285	pathogenic	-0.714	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/Y	0.8431	likely_pathogenic	0.8372	pathogenic	-0.364	Destabilizing	0.999	D	0.831	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.