TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17259	52000;52001;52002	chr2:178609535;178609534;178609533	chr2:179474262;179474261;179474260
N2AB	15618	47077;47078;47079	chr2:178609535;178609534;178609533	chr2:179474262;179474261;179474260
N2A	14691	44296;44297;44298	chr2:178609535;178609534;178609533	chr2:179474262;179474261;179474260
N2B	8194	24805;24806;24807	chr2:178609535;178609534;178609533	chr2:179474262;179474261;179474260
Novex-1	8319	25180;25181;25182	chr2:178609535;178609534;178609533	chr2:179474262;179474261;179474260
Novex-2	8386	25381;25382;25383	chr2:178609535;178609534;178609533	chr2:179474262;179474261;179474260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-112
• Domain position: 9
• Structural Position: 16
• Q(SASA): 0.16
• 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
V/M	None	None	1.0	D	0.761	0.569	0.686737365345	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

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
V/A	0.5542	ambiguous	0.5083	ambiguous	-1.857	Destabilizing	0.999	D	0.503	neutral	D	0.534062409	None	None	N
V/C	0.8577	likely_pathogenic	0.8594	pathogenic	-1.525	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
V/D	0.9674	likely_pathogenic	0.9491	pathogenic	-1.835	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/E	0.9047	likely_pathogenic	0.8616	pathogenic	-1.755	Destabilizing	1.0	D	0.785	deleterious	N	0.50934149	None	None	N
V/F	0.6087	likely_pathogenic	0.5737	pathogenic	-1.315	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
V/G	0.6503	likely_pathogenic	0.5904	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.786	deleterious	D	0.535421462	None	None	N
V/H	0.9714	likely_pathogenic	0.9591	pathogenic	-1.774	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
V/I	0.1029	likely_benign	0.1049	benign	-0.82	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	N
V/K	0.906	likely_pathogenic	0.8604	pathogenic	-1.478	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
V/L	0.6254	likely_pathogenic	0.6261	pathogenic	-0.82	Destabilizing	0.997	D	0.504	neutral	N	0.498564161	None	None	N
V/M	0.4807	ambiguous	0.4692	ambiguous	-0.816	Destabilizing	1.0	D	0.761	deleterious	D	0.535167973	None	None	N
V/N	0.9026	likely_pathogenic	0.8673	pathogenic	-1.46	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/P	0.9887	likely_pathogenic	0.9816	pathogenic	-1.134	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
V/Q	0.8891	likely_pathogenic	0.8466	pathogenic	-1.538	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/R	0.8775	likely_pathogenic	0.8247	pathogenic	-1.07	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/S	0.7872	likely_pathogenic	0.7456	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/T	0.5439	ambiguous	0.5003	ambiguous	-1.889	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
V/W	0.985	likely_pathogenic	0.9811	pathogenic	-1.573	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
V/Y	0.9237	likely_pathogenic	0.9044	pathogenic	-1.256	Destabilizing	1.0	D	0.801	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.