TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3414	10465;10466;10467	chr2:178759047;178759046;178759045	chr2:179623774;179623773;179623772
N2AB	3414	10465;10466;10467	chr2:178759047;178759046;178759045	chr2:179623774;179623773;179623772
N2A	3414	10465;10466;10467	chr2:178759047;178759046;178759045	chr2:179623774;179623773;179623772
N2B	3368	10327;10328;10329	chr2:178759047;178759046;178759045	chr2:179623774;179623773;179623772
Novex-1	3368	10327;10328;10329	chr2:178759047;178759046;178759045	chr2:179623774;179623773;179623772
Novex-2	3368	10327;10328;10329	chr2:178759047;178759046;178759045	chr2:179623774;179623773;179623772
Novex-3	3414	10465;10466;10467	chr2:178759047;178759046;178759045	chr2:179623774;179623773;179623772

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-24
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.1102
• 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
Y/C	None	None	1.0	D	0.859	0.912	0.93233676213	gnomAD-4.0.0	1.59076E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02188E-05
Y/D	None	None	1.0	D	0.887	0.923	0.948424836998	gnomAD-4.0.0	1.20036E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31255E-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
Y/A	0.9897	likely_pathogenic	0.9903	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
Y/C	0.7868	likely_pathogenic	0.8257	pathogenic	-1.536	Destabilizing	1.0	D	0.859	deleterious	D	0.77922468	None	None	N
Y/D	0.9971	likely_pathogenic	0.9974	pathogenic	-2.736	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.779326511	None	None	N
Y/E	0.9987	likely_pathogenic	0.9989	pathogenic	-2.484	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/F	0.169	likely_benign	0.2108	benign	-0.71	Destabilizing	0.999	D	0.688	prob.neutral	D	0.588526407	None	None	N
Y/G	0.9904	likely_pathogenic	0.9911	pathogenic	-2.66	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/H	0.9509	likely_pathogenic	0.9656	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.789	deleterious	D	0.779428523	None	None	N
Y/I	0.8815	likely_pathogenic	0.8879	pathogenic	-0.682	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/K	0.9977	likely_pathogenic	0.9982	pathogenic	-1.637	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
Y/L	0.8271	likely_pathogenic	0.8309	pathogenic	-0.682	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
Y/M	0.9615	likely_pathogenic	0.9651	pathogenic	-0.824	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/N	0.9821	likely_pathogenic	0.9829	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.77922468	None	None	N
Y/P	0.998	likely_pathogenic	0.9977	pathogenic	-1.204	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/Q	0.9972	likely_pathogenic	0.9979	pathogenic	-2.088	Highly Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
Y/R	0.9903	likely_pathogenic	0.992	pathogenic	-1.915	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/S	0.9785	likely_pathogenic	0.9783	pathogenic	-2.873	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.77922468	None	None	N
Y/T	0.9898	likely_pathogenic	0.9894	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/V	0.8015	likely_pathogenic	0.8014	pathogenic	-1.204	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/W	0.7321	likely_pathogenic	0.7291	pathogenic	-0.064	Destabilizing	1.0	D	0.779	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.