TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7585	22978;22979;22980	chr2:178721910;178721909;178721908	chr2:179586637;179586636;179586635
N2AB	7268	22027;22028;22029	chr2:178721910;178721909;178721908	chr2:179586637;179586636;179586635
N2A	6341	19246;19247;19248	chr2:178721910;178721909;178721908	chr2:179586637;179586636;179586635
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-60
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0878
• 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	0.873	0.767	0.889184030382	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
Y/A	0.9983	likely_pathogenic	0.9986	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/C	0.9897	likely_pathogenic	0.9879	pathogenic	-1.311	Destabilizing	1.0	D	0.873	deleterious	D	0.662013488	None	None	N
Y/D	0.9991	likely_pathogenic	0.9992	pathogenic	-2.769	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.662013488	None	None	N
Y/E	0.9995	likely_pathogenic	0.9995	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/F	0.2928	likely_benign	0.3146	benign	-0.787	Destabilizing	0.999	D	0.684	prob.neutral	D	0.569017262	None	None	N
Y/G	0.9964	likely_pathogenic	0.997	pathogenic	-2.524	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/H	0.9926	likely_pathogenic	0.9947	pathogenic	-2.214	Highly Destabilizing	1.0	D	0.794	deleterious	D	0.645792323	None	None	N
Y/I	0.9359	likely_pathogenic	0.9196	pathogenic	-0.645	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
Y/K	0.9995	likely_pathogenic	0.9996	pathogenic	-1.517	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/L	0.8959	likely_pathogenic	0.9078	pathogenic	-0.645	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
Y/M	0.9854	likely_pathogenic	0.9849	pathogenic	-0.79	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
Y/N	0.9942	likely_pathogenic	0.9948	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.662013488	None	None	N
Y/P	0.9995	likely_pathogenic	0.9995	pathogenic	-1.143	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/Q	0.9995	likely_pathogenic	0.9996	pathogenic	-1.938	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.998	likely_pathogenic	0.9983	pathogenic	-1.901	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/S	0.9972	likely_pathogenic	0.9977	pathogenic	-2.628	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.662013488	None	None	N
Y/T	0.9986	likely_pathogenic	0.9988	pathogenic	-2.237	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9205	likely_pathogenic	0.9087	pathogenic	-1.143	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/W	0.9176	likely_pathogenic	0.9377	pathogenic	-0.207	Destabilizing	1.0	D	0.787	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.