TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3266	10021;10022;10023	chr2:178764719;178764718;178764717	chr2:179629446;179629445;179629444
N2AB	3266	10021;10022;10023	chr2:178764719;178764718;178764717	chr2:179629446;179629445;179629444
N2A	3266	10021;10022;10023	chr2:178764719;178764718;178764717	chr2:179629446;179629445;179629444
N2B	3220	9883;9884;9885	chr2:178764719;178764718;178764717	chr2:179629446;179629445;179629444
Novex-1	3220	9883;9884;9885	chr2:178764719;178764718;178764717	chr2:179629446;179629445;179629444
Novex-2	3220	9883;9884;9885	chr2:178764719;178764718;178764717	chr2:179629446;179629445;179629444
Novex-3	3266	10021;10022;10023	chr2:178764719;178764718;178764717	chr2:179629446;179629445;179629444

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-23
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.5034
• 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
P/L	None	None	1.0	D	0.767	0.756	0.904293489814	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/S	rs2090043271	None	1.0	D	0.757	0.739	0.669000193909	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	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
P/A	0.9082	likely_pathogenic	0.9807	pathogenic	-1.027	Destabilizing	1.0	D	0.754	deleterious	D	0.813362886	None	None	I
P/C	0.9949	likely_pathogenic	0.9989	pathogenic	-0.438	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
P/D	0.9873	likely_pathogenic	0.9962	pathogenic	-0.855	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/E	0.9726	likely_pathogenic	0.9945	pathogenic	-0.918	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/F	0.9961	likely_pathogenic	0.9992	pathogenic	-0.993	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
P/G	0.9737	likely_pathogenic	0.9909	pathogenic	-1.253	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
P/H	0.9762	likely_pathogenic	0.9956	pathogenic	-0.871	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/I	0.9716	likely_pathogenic	0.9946	pathogenic	-0.539	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/K	0.9799	likely_pathogenic	0.9964	pathogenic	-0.829	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
P/L	0.9204	likely_pathogenic	0.9853	pathogenic	-0.539	Destabilizing	1.0	D	0.767	deleterious	D	0.829655399	None	None	I
P/M	0.9791	likely_pathogenic	0.9964	pathogenic	-0.348	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/N	0.9843	likely_pathogenic	0.9956	pathogenic	-0.432	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/Q	0.9604	likely_pathogenic	0.9935	pathogenic	-0.661	Destabilizing	1.0	D	0.784	deleterious	D	0.757994927	None	None	I
P/R	0.9604	likely_pathogenic	0.9923	pathogenic	-0.288	Destabilizing	1.0	D	0.791	deleterious	D	0.813827173	None	None	I
P/S	0.9658	likely_pathogenic	0.994	pathogenic	-0.81	Destabilizing	1.0	D	0.757	deleterious	D	0.756798279	None	None	I
P/T	0.9242	likely_pathogenic	0.9868	pathogenic	-0.778	Destabilizing	1.0	D	0.755	deleterious	D	0.779214241	None	None	I
P/V	0.9444	likely_pathogenic	0.9868	pathogenic	-0.667	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/W	0.9975	likely_pathogenic	0.9995	pathogenic	-1.134	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
P/Y	0.9932	likely_pathogenic	0.9984	pathogenic	-0.858	Destabilizing	1.0	D	0.817	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.