TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5533	16822;16823;16824	chr2:178732464;178732463;178732462	chr2:179597191;179597190;179597189
N2AB	5216	15871;15872;15873	chr2:178732464;178732463;178732462	chr2:179597191;179597190;179597189
N2A	4289	13090;13091;13092	chr2:178732464;178732463;178732462	chr2:179597191;179597190;179597189
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-38
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.0994
• 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
C/F	None	None	0.484	D	0.773	0.353	0.683392867763	gnomAD-4.0.0	1.59869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87305E-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
C/A	0.428	ambiguous	0.4248	ambiguous	-1.836	Destabilizing	0.035	N	0.518	neutral	None	None	None	None	N
C/D	0.6836	likely_pathogenic	0.7114	pathogenic	-0.506	Destabilizing	0.081	N	0.796	deleterious	None	None	None	None	N
C/E	0.8749	likely_pathogenic	0.8772	pathogenic	-0.386	Destabilizing	0.235	N	0.799	deleterious	None	None	None	None	N
C/F	0.3754	ambiguous	0.3866	ambiguous	-1.132	Destabilizing	0.484	N	0.773	deleterious	D	0.533635547	None	None	N
C/G	0.2557	likely_benign	0.2612	benign	-2.159	Highly Destabilizing	None	N	0.54	neutral	N	0.485630331	None	None	N
C/H	0.7429	likely_pathogenic	0.7488	pathogenic	-2.124	Highly Destabilizing	0.824	D	0.76	deleterious	None	None	None	None	N
C/I	0.6189	likely_pathogenic	0.6135	pathogenic	-0.995	Destabilizing	0.38	N	0.784	deleterious	None	None	None	None	N
C/K	0.9327	likely_pathogenic	0.932	pathogenic	-1.084	Destabilizing	0.235	N	0.796	deleterious	None	None	None	None	N
C/L	0.661	likely_pathogenic	0.6472	pathogenic	-0.995	Destabilizing	0.149	N	0.718	prob.delet.	None	None	None	None	N
C/M	0.7211	likely_pathogenic	0.7033	pathogenic	-0.025	Destabilizing	0.935	D	0.729	prob.delet.	None	None	None	None	N
C/N	0.6178	likely_pathogenic	0.6386	pathogenic	-1.115	Destabilizing	0.235	N	0.801	deleterious	None	None	None	None	N
C/P	0.9941	likely_pathogenic	0.9937	pathogenic	-1.25	Destabilizing	0.38	N	0.797	deleterious	None	None	None	None	N
C/Q	0.8141	likely_pathogenic	0.8059	pathogenic	-0.987	Destabilizing	0.38	N	0.806	deleterious	None	None	None	None	N
C/R	0.7459	likely_pathogenic	0.7439	pathogenic	-0.975	Destabilizing	0.317	N	0.807	deleterious	N	0.509411893	None	None	N
C/S	0.2906	likely_benign	0.2959	benign	-1.668	Destabilizing	None	N	0.405	neutral	N	0.441320032	None	None	N
C/T	0.4218	ambiguous	0.3942	ambiguous	-1.362	Destabilizing	0.081	N	0.715	prob.delet.	None	None	None	None	N
C/V	0.5082	ambiguous	0.4879	ambiguous	-1.25	Destabilizing	0.149	N	0.736	prob.delet.	None	None	None	None	N
C/W	0.7414	likely_pathogenic	0.7501	pathogenic	-1.138	Destabilizing	0.915	D	0.721	prob.delet.	N	0.490505403	None	None	N
C/Y	0.5052	ambiguous	0.531	ambiguous	-1.131	Destabilizing	0.484	N	0.744	deleterious	N	0.51872481	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.