TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20028	60307;60308;60309	chr2:178591737;178591736;178591735	chr2:179456464;179456463;179456462
N2AB	18387	55384;55385;55386	chr2:178591737;178591736;178591735	chr2:179456464;179456463;179456462
N2A	17460	52603;52604;52605	chr2:178591737;178591736;178591735	chr2:179456464;179456463;179456462
N2B	10963	33112;33113;33114	chr2:178591737;178591736;178591735	chr2:179456464;179456463;179456462
Novex-1	11088	33487;33488;33489	chr2:178591737;178591736;178591735	chr2:179456464;179456463;179456462
Novex-2	11155	33688;33689;33690	chr2:178591737;178591736;178591735	chr2:179456464;179456463;179456462
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: Fn3-33
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.4419
• 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	0.993	N	0.672	0.199	0.247872288689	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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	0.4138	ambiguous	0.4415	ambiguous	-0.227	Destabilizing	0.983	D	0.589	neutral	None	None	None	None	N
K/C	0.6599	likely_pathogenic	0.717	pathogenic	-0.555	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/D	0.6405	likely_pathogenic	0.6617	pathogenic	0.036	Stabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	N
K/E	0.1933	likely_benign	0.1966	benign	0.111	Stabilizing	0.955	D	0.512	neutral	N	0.450024368	None	None	N
K/F	0.892	likely_pathogenic	0.9188	pathogenic	-0.209	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/G	0.546	ambiguous	0.583	pathogenic	-0.494	Destabilizing	0.995	D	0.623	neutral	None	None	None	None	N
K/H	0.3298	likely_benign	0.3432	ambiguous	-0.625	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
K/I	0.5888	likely_pathogenic	0.6298	pathogenic	0.425	Stabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
K/L	0.4918	ambiguous	0.524	ambiguous	0.425	Stabilizing	0.995	D	0.623	neutral	None	None	None	None	N
K/M	0.3232	likely_benign	0.3475	ambiguous	-0.03	Destabilizing	0.999	D	0.709	prob.delet.	N	0.471635501	None	None	N
K/N	0.4599	ambiguous	0.49	ambiguous	-0.252	Destabilizing	0.993	D	0.672	neutral	N	0.436169636	None	None	N
K/P	0.9364	likely_pathogenic	0.9575	pathogenic	0.236	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
K/Q	0.1098	likely_benign	0.1072	benign	-0.27	Destabilizing	0.568	D	0.29	neutral	N	0.503088062	None	None	N
K/R	0.0933	likely_benign	0.0981	benign	-0.227	Destabilizing	0.955	D	0.526	neutral	N	0.492948426	None	None	N
K/S	0.4116	ambiguous	0.4332	ambiguous	-0.759	Destabilizing	0.983	D	0.567	neutral	None	None	None	None	N
K/T	0.2042	likely_benign	0.2123	benign	-0.502	Destabilizing	0.993	D	0.699	prob.neutral	N	0.473898518	None	None	N
K/V	0.5052	ambiguous	0.5438	ambiguous	0.236	Stabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
K/W	0.8671	likely_pathogenic	0.9033	pathogenic	-0.223	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/Y	0.7265	likely_pathogenic	0.7896	pathogenic	0.108	Stabilizing	0.999	D	0.697	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.