TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26403	79432;79433;79434	chr2:178566925;178566924;178566923	chr2:179431652;179431651;179431650
N2AB	24762	74509;74510;74511	chr2:178566925;178566924;178566923	chr2:179431652;179431651;179431650
N2A	23835	71728;71729;71730	chr2:178566925;178566924;178566923	chr2:179431652;179431651;179431650
N2B	17338	52237;52238;52239	chr2:178566925;178566924;178566923	chr2:179431652;179431651;179431650
Novex-1	17463	52612;52613;52614	chr2:178566925;178566924;178566923	chr2:179431652;179431651;179431650
Novex-2	17530	52813;52814;52815	chr2:178566925;178566924;178566923	chr2:179431652;179431651;179431650
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-80
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.059
• 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
M/I	rs1706091561	None	0.985	N	0.641	0.417	0.50857664894	gnomAD-4.0.0	6.84282E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99539E-07	0	0
M/K	rs1469438235	-0.272	0.994	N	0.795	0.65	0.681219007559	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
M/K	rs1469438235	-0.272	0.994	N	0.795	0.65	0.681219007559	gnomAD-4.0.0	4.77483E-06	None	None	None	None	N	None	0	6.86091E-05	None	0	0	None	0	0	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
M/A	0.8647	likely_pathogenic	0.834	pathogenic	-2.024	Highly Destabilizing	0.989	D	0.697	prob.neutral	None	None	None	None	N
M/C	0.9002	likely_pathogenic	0.9038	pathogenic	-2.515	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
M/D	0.9997	likely_pathogenic	0.9996	pathogenic	-2.003	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
M/E	0.9972	likely_pathogenic	0.9957	pathogenic	-1.743	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
M/F	0.8932	likely_pathogenic	0.8837	pathogenic	-0.644	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
M/G	0.9907	likely_pathogenic	0.9888	pathogenic	-2.53	Highly Destabilizing	0.995	D	0.768	deleterious	None	None	None	None	N
M/H	0.9981	likely_pathogenic	0.9974	pathogenic	-2.337	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
M/I	0.8609	likely_pathogenic	0.7779	pathogenic	-0.563	Destabilizing	0.985	D	0.641	neutral	N	0.419584031	None	None	N
M/K	0.994	likely_pathogenic	0.9907	pathogenic	-1.193	Destabilizing	0.994	D	0.795	deleterious	N	0.510148189	None	None	N
M/L	0.5764	likely_pathogenic	0.5132	ambiguous	-0.563	Destabilizing	0.927	D	0.434	neutral	N	0.457174053	None	None	N
M/N	0.9968	likely_pathogenic	0.9956	pathogenic	-1.689	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
M/P	0.9997	likely_pathogenic	0.9996	pathogenic	-1.032	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
M/Q	0.969	likely_pathogenic	0.9636	pathogenic	-1.296	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
M/R	0.9933	likely_pathogenic	0.99	pathogenic	-1.51	Destabilizing	0.998	D	0.83	deleterious	N	0.498627299	None	None	N
M/S	0.9703	likely_pathogenic	0.9623	pathogenic	-2.234	Highly Destabilizing	0.995	D	0.767	deleterious	None	None	None	None	N
M/T	0.9656	likely_pathogenic	0.9483	pathogenic	-1.829	Destabilizing	0.994	D	0.79	deleterious	N	0.483143164	None	None	N
M/V	0.3195	likely_benign	0.2471	benign	-1.032	Destabilizing	0.985	D	0.535	neutral	N	0.39789925	None	None	N
M/W	0.9977	likely_pathogenic	0.9973	pathogenic	-0.994	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
M/Y	0.9949	likely_pathogenic	0.994	pathogenic	-0.928	Destabilizing	0.999	D	0.829	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.