TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29212	87859;87860;87861	chr2:178557720;178557719;178557718	chr2:179422447;179422446;179422445
N2AB	27571	82936;82937;82938	chr2:178557720;178557719;178557718	chr2:179422447;179422446;179422445
N2A	26644	80155;80156;80157	chr2:178557720;178557719;178557718	chr2:179422447;179422446;179422445
N2B	20147	60664;60665;60666	chr2:178557720;178557719;178557718	chr2:179422447;179422446;179422445
Novex-1	20272	61039;61040;61041	chr2:178557720;178557719;178557718	chr2:179422447;179422446;179422445
Novex-2	20339	61240;61241;61242	chr2:178557720;178557719;178557718	chr2:179422447;179422446;179422445
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-100
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0611
• 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
I/M	None	None	0.995	N	0.65	0.535	0.579560680208	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85776E-06	0	0
I/V	None	None	0.878	N	0.271	0.192	0.277730125212	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
I/A	0.9475	likely_pathogenic	0.9637	pathogenic	-3.27	Highly Destabilizing	0.919	D	0.635	neutral	None	None	None	None	N
I/C	0.9347	likely_pathogenic	0.95	pathogenic	-2.565	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
I/D	0.9995	likely_pathogenic	0.9995	pathogenic	-4.01	Highly Destabilizing	0.034	N	0.737	prob.delet.	None	None	None	None	N
I/E	0.9979	likely_pathogenic	0.9978	pathogenic	-3.717	Highly Destabilizing	0.851	D	0.835	deleterious	None	None	None	None	N
I/F	0.7619	likely_pathogenic	0.7955	pathogenic	-1.996	Destabilizing	0.995	D	0.583	neutral	N	0.509964513	None	None	N
I/G	0.9917	likely_pathogenic	0.9934	pathogenic	-3.815	Highly Destabilizing	0.976	D	0.835	deleterious	None	None	None	None	N
I/H	0.9979	likely_pathogenic	0.9978	pathogenic	-3.352	Highly Destabilizing	0.999	D	0.882	deleterious	None	None	None	None	N
I/K	0.9955	likely_pathogenic	0.9957	pathogenic	-2.808	Highly Destabilizing	0.976	D	0.855	deleterious	None	None	None	None	N
I/L	0.3286	likely_benign	0.3652	ambiguous	-1.608	Destabilizing	0.878	D	0.347	neutral	N	0.470358508	None	None	N
I/M	0.4139	ambiguous	0.4699	ambiguous	-1.747	Destabilizing	0.995	D	0.65	neutral	N	0.510218003	None	None	N
I/N	0.9908	likely_pathogenic	0.9914	pathogenic	-3.458	Highly Destabilizing	0.938	D	0.863	deleterious	D	0.528829237	None	None	N
I/P	0.9968	likely_pathogenic	0.9971	pathogenic	-2.157	Highly Destabilizing	0.988	D	0.881	deleterious	None	None	None	None	N
I/Q	0.9955	likely_pathogenic	0.9958	pathogenic	-3.173	Highly Destabilizing	0.988	D	0.891	deleterious	None	None	None	None	N
I/R	0.9928	likely_pathogenic	0.993	pathogenic	-2.593	Highly Destabilizing	0.988	D	0.893	deleterious	None	None	None	None	N
I/S	0.9832	likely_pathogenic	0.9861	pathogenic	-3.976	Highly Destabilizing	0.896	D	0.799	deleterious	N	0.517472932	None	None	N
I/T	0.9715	likely_pathogenic	0.9754	pathogenic	-3.548	Highly Destabilizing	0.946	D	0.71	prob.delet.	N	0.510471492	None	None	N
I/V	0.1063	likely_benign	0.1111	benign	-2.157	Highly Destabilizing	0.878	D	0.271	neutral	N	0.380144916	None	None	N
I/W	0.9959	likely_pathogenic	0.996	pathogenic	-2.421	Highly Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
I/Y	0.982	likely_pathogenic	0.9829	pathogenic	-2.31	Highly Destabilizing	0.996	D	0.749	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.