TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8541	25846;25847;25848	chr2:178717113;178717112;178717111	chr2:179581840;179581839;179581838
N2AB	8224	24895;24896;24897	chr2:178717113;178717112;178717111	chr2:179581840;179581839;179581838
N2A	7297	22114;22115;22116	chr2:178717113;178717112;178717111	chr2:179581840;179581839;179581838
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-70
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1702
• 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
A/V	None	None	0.511	N	0.39	0.253	0.472582640538	gnomAD-4.0.0	1.59535E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86776E-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
A/C	0.7202	likely_pathogenic	0.7425	pathogenic	-1.269	Destabilizing	0.349	N	0.427	neutral	None	None	None	None	N
A/D	0.9368	likely_pathogenic	0.95	pathogenic	-1.398	Destabilizing	0.987	D	0.786	deleterious	D	0.556840172	None	None	N
A/E	0.9318	likely_pathogenic	0.9443	pathogenic	-1.339	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
A/F	0.8314	likely_pathogenic	0.8707	pathogenic	-0.976	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
A/G	0.2166	likely_benign	0.2393	benign	-1.369	Destabilizing	0.679	D	0.607	neutral	N	0.495525968	None	None	N
A/H	0.9563	likely_pathogenic	0.9658	pathogenic	-1.563	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/I	0.6602	likely_pathogenic	0.7085	pathogenic	-0.146	Destabilizing	0.993	D	0.729	prob.delet.	None	None	None	None	N
A/K	0.9805	likely_pathogenic	0.9854	pathogenic	-1.121	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
A/L	0.5983	likely_pathogenic	0.6499	pathogenic	-0.146	Destabilizing	0.993	D	0.662	neutral	None	None	None	None	N
A/M	0.6249	likely_pathogenic	0.6673	pathogenic	-0.292	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
A/N	0.8913	likely_pathogenic	0.9103	pathogenic	-1.076	Destabilizing	0.922	D	0.782	deleterious	None	None	None	None	N
A/P	0.9831	likely_pathogenic	0.9866	pathogenic	-0.39	Destabilizing	0.994	D	0.769	deleterious	D	0.538900501	None	None	N
A/Q	0.9093	likely_pathogenic	0.927	pathogenic	-1.106	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
A/R	0.9468	likely_pathogenic	0.9585	pathogenic	-0.972	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
A/S	0.1398	likely_benign	0.1442	benign	-1.56	Destabilizing	0.026	N	0.173	neutral	N	0.50691588	None	None	N
A/T	0.1812	likely_benign	0.1885	benign	-1.378	Destabilizing	0.877	D	0.611	neutral	N	0.49318211	None	None	N
A/V	0.3294	likely_benign	0.3622	ambiguous	-0.39	Destabilizing	0.511	D	0.39	neutral	N	0.50333407	None	None	N
A/W	0.984	likely_pathogenic	0.9889	pathogenic	-1.427	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/Y	0.946	likely_pathogenic	0.96	pathogenic	-0.949	Destabilizing	1.0	D	0.784	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.