TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5403	16432;16433;16434	chr2:178732969;178732968;178732967	chr2:179597696;179597695;179597694
N2AB	5086	15481;15482;15483	chr2:178732969;178732968;178732967	chr2:179597696;179597695;179597694
N2A	4159	12700;12701;12702	chr2:178732969;178732968;178732967	chr2:179597696;179597695;179597694
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: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-37
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2048
• 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/F	None	None	0.003	N	0.175	0.231	0.333154297509	gnomAD-4.0.0	1.59173E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-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
Y/A	0.6392	likely_pathogenic	0.6665	pathogenic	-2.669	Highly Destabilizing	0.742	D	0.531	neutral	None	None	None	None	N
Y/C	0.1678	likely_benign	0.1732	benign	-1.77	Destabilizing	0.994	D	0.557	neutral	N	0.513448731	None	None	N
Y/D	0.5704	likely_pathogenic	0.5764	pathogenic	-1.93	Destabilizing	0.939	D	0.618	neutral	N	0.519551571	None	None	N
Y/E	0.7399	likely_pathogenic	0.7522	pathogenic	-1.747	Destabilizing	0.742	D	0.553	neutral	None	None	None	None	N
Y/F	0.1262	likely_benign	0.1394	benign	-0.94	Destabilizing	0.003	N	0.175	neutral	N	0.507411738	None	None	N
Y/G	0.5123	ambiguous	0.5321	ambiguous	-3.082	Highly Destabilizing	0.854	D	0.6	neutral	None	None	None	None	N
Y/H	0.1865	likely_benign	0.2016	benign	-1.556	Destabilizing	0.015	N	0.37	neutral	D	0.526941648	None	None	N
Y/I	0.4999	ambiguous	0.5316	ambiguous	-1.346	Destabilizing	0.59	D	0.537	neutral	None	None	None	None	N
Y/K	0.7002	likely_pathogenic	0.6996	pathogenic	-1.907	Destabilizing	0.59	D	0.539	neutral	None	None	None	None	N
Y/L	0.4332	ambiguous	0.4524	ambiguous	-1.346	Destabilizing	0.373	N	0.489	neutral	None	None	None	None	N
Y/M	0.663	likely_pathogenic	0.6907	pathogenic	-1.208	Destabilizing	0.953	D	0.564	neutral	None	None	None	None	N
Y/N	0.235	likely_benign	0.2517	benign	-2.536	Highly Destabilizing	0.884	D	0.587	neutral	N	0.511562627	None	None	N
Y/P	0.9274	likely_pathogenic	0.9206	pathogenic	-1.793	Destabilizing	0.984	D	0.632	neutral	None	None	None	None	N
Y/Q	0.5372	ambiguous	0.5467	ambiguous	-2.27	Highly Destabilizing	0.91	D	0.577	neutral	None	None	None	None	N
Y/R	0.5108	ambiguous	0.5103	ambiguous	-1.685	Destabilizing	0.009	N	0.401	neutral	None	None	None	None	N
Y/S	0.3163	likely_benign	0.3328	benign	-3.088	Highly Destabilizing	0.684	D	0.552	neutral	N	0.501585447	None	None	N
Y/T	0.533	ambiguous	0.5612	ambiguous	-2.783	Highly Destabilizing	0.854	D	0.55	neutral	None	None	None	None	N
Y/V	0.4142	ambiguous	0.4462	ambiguous	-1.793	Destabilizing	0.742	D	0.508	neutral	None	None	None	None	N
Y/W	0.485	ambiguous	0.5074	ambiguous	-0.313	Destabilizing	0.984	D	0.565	neutral	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.