TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26436	79531;79532;79533	chr2:178566826;178566825;178566824	chr2:179431553;179431552;179431551
N2AB	24795	74608;74609;74610	chr2:178566826;178566825;178566824	chr2:179431553;179431552;179431551
N2A	23868	71827;71828;71829	chr2:178566826;178566825;178566824	chr2:179431553;179431552;179431551
N2B	17371	52336;52337;52338	chr2:178566826;178566825;178566824	chr2:179431553;179431552;179431551
Novex-1	17496	52711;52712;52713	chr2:178566826;178566825;178566824	chr2:179431553;179431552;179431551
Novex-2	17563	52912;52913;52914	chr2:178566826;178566825;178566824	chr2:179431553;179431552;179431551
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-80
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2588
• 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/R	None	None	0.97	N	0.803	0.525	0.783465323079	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
C/Y	None	None	0.97	N	0.777	0.546	0.661029647469	gnomAD-4.0.0	2.7375E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	0	1.15937E-05	3.31422E-05

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	0.7099	likely_pathogenic	0.7039	pathogenic	-1.567	Destabilizing	0.559	D	0.475	neutral	None	None	None	None	N
C/D	0.9974	likely_pathogenic	0.9981	pathogenic	-0.123	Destabilizing	0.993	D	0.799	deleterious	None	None	None	None	N
C/E	0.9979	likely_pathogenic	0.9984	pathogenic	-0.03	Destabilizing	0.978	D	0.805	deleterious	None	None	None	None	N
C/F	0.9057	likely_pathogenic	0.9334	pathogenic	-0.944	Destabilizing	0.942	D	0.769	deleterious	N	0.473642828	None	None	N
C/G	0.6881	likely_pathogenic	0.716	pathogenic	-1.865	Destabilizing	0.97	D	0.736	prob.delet.	N	0.499054918	None	None	N
C/H	0.9873	likely_pathogenic	0.9923	pathogenic	-1.794	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
C/I	0.8109	likely_pathogenic	0.7992	pathogenic	-0.809	Destabilizing	0.754	D	0.52	neutral	None	None	None	None	N
C/K	0.9989	likely_pathogenic	0.9992	pathogenic	-0.849	Destabilizing	0.978	D	0.783	deleterious	None	None	None	None	N
C/L	0.8855	likely_pathogenic	0.8956	pathogenic	-0.809	Destabilizing	0.559	D	0.54	neutral	None	None	None	None	N
C/M	0.9328	likely_pathogenic	0.9377	pathogenic	0.067	Stabilizing	0.978	D	0.733	prob.delet.	None	None	None	None	N
C/N	0.9675	likely_pathogenic	0.9736	pathogenic	-0.835	Destabilizing	0.993	D	0.807	deleterious	None	None	None	None	N
C/P	0.9957	likely_pathogenic	0.9958	pathogenic	-1.035	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
C/Q	0.9906	likely_pathogenic	0.9931	pathogenic	-0.729	Destabilizing	0.993	D	0.797	deleterious	None	None	None	None	N
C/R	0.9904	likely_pathogenic	0.9931	pathogenic	-0.688	Destabilizing	0.97	D	0.803	deleterious	N	0.520157687	None	None	N
C/S	0.7574	likely_pathogenic	0.7669	pathogenic	-1.385	Destabilizing	0.904	D	0.63	neutral	N	0.486684655	None	None	N
C/T	0.8383	likely_pathogenic	0.8269	pathogenic	-1.109	Destabilizing	0.86	D	0.585	neutral	None	None	None	None	N
C/V	0.5604	ambiguous	0.5332	ambiguous	-1.035	Destabilizing	0.019	N	0.367	neutral	None	None	None	None	N
C/W	0.9836	likely_pathogenic	0.9895	pathogenic	-0.929	Destabilizing	0.997	D	0.755	deleterious	D	0.522946071	None	None	N
C/Y	0.9533	likely_pathogenic	0.9685	pathogenic	-0.915	Destabilizing	0.97	D	0.777	deleterious	N	0.494927088	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.