TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26378	79357;79358;79359	chr2:178567000;178566999;178566998	chr2:179431727;179431726;179431725
N2AB	24737	74434;74435;74436	chr2:178567000;178566999;178566998	chr2:179431727;179431726;179431725
N2A	23810	71653;71654;71655	chr2:178567000;178566999;178566998	chr2:179431727;179431726;179431725
N2B	17313	52162;52163;52164	chr2:178567000;178566999;178566998	chr2:179431727;179431726;179431725
Novex-1	17438	52537;52538;52539	chr2:178567000;178566999;178566998	chr2:179431727;179431726;179431725
Novex-2	17505	52738;52739;52740	chr2:178567000;178566999;178566998	chr2:179431727;179431726;179431725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-79
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.2795
• Predicted PPI site: I

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/I	rs1476994621	-0.547	0.994	N	0.693	0.241	0.354822389136	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
V/I	rs1476994621	-0.547	0.994	N	0.693	0.241	0.354822389136	gnomAD-4.0.0	1.36855E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99551E-07	1.15934E-05	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	0.4084	ambiguous	0.392	ambiguous	-1.723	Destabilizing	0.997	D	0.717	prob.delet.	N	0.507902782	None	None	I
V/C	0.7606	likely_pathogenic	0.7482	pathogenic	-1.016	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
V/D	0.9296	likely_pathogenic	0.9231	pathogenic	-2.165	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	I
V/E	0.7589	likely_pathogenic	0.7393	pathogenic	-1.996	Destabilizing	0.999	D	0.885	deleterious	N	0.520944608	None	None	I
V/F	0.3178	likely_benign	0.2935	benign	-1.068	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	I
V/G	0.6678	likely_pathogenic	0.6496	pathogenic	-2.19	Highly Destabilizing	0.999	D	0.847	deleterious	N	0.520944608	None	None	I
V/H	0.8722	likely_pathogenic	0.8586	pathogenic	-1.821	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
V/I	0.0788	likely_benign	0.0762	benign	-0.452	Destabilizing	0.994	D	0.693	prob.delet.	N	0.458563707	None	None	I
V/K	0.7653	likely_pathogenic	0.7702	pathogenic	-1.496	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	I
V/L	0.2336	likely_benign	0.2166	benign	-0.452	Destabilizing	0.994	D	0.692	prob.delet.	N	0.476921284	None	None	I
V/M	0.1741	likely_benign	0.1697	benign	-0.312	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
V/N	0.8057	likely_pathogenic	0.7835	pathogenic	-1.678	Destabilizing	0.999	D	0.901	deleterious	None	None	None	None	I
V/P	0.9858	likely_pathogenic	0.981	pathogenic	-0.847	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	I
V/Q	0.6569	likely_pathogenic	0.6415	pathogenic	-1.617	Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	I
V/R	0.7285	likely_pathogenic	0.7331	pathogenic	-1.206	Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	I
V/S	0.6106	likely_pathogenic	0.5883	pathogenic	-2.231	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	I
V/T	0.3485	ambiguous	0.3406	ambiguous	-1.931	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	I
V/W	0.9537	likely_pathogenic	0.9416	pathogenic	-1.537	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
V/Y	0.8025	likely_pathogenic	0.7868	pathogenic	-1.114	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	I

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.