TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19739	59440;59441;59442	chr2:178592904;178592903;178592902	chr2:179457631;179457630;179457629
N2AB	18098	54517;54518;54519	chr2:178592904;178592903;178592902	chr2:179457631;179457630;179457629
N2A	17171	51736;51737;51738	chr2:178592904;178592903;178592902	chr2:179457631;179457630;179457629
N2B	10674	32245;32246;32247	chr2:178592904;178592903;178592902	chr2:179457631;179457630;179457629
Novex-1	10799	32620;32621;32622	chr2:178592904;178592903;178592902	chr2:179457631;179457630;179457629
Novex-2	10866	32821;32822;32823	chr2:178592904;178592903;178592902	chr2:179457631;179457630;179457629
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-31
• Domain position: 60
• Structural Position: 88
• Q(SASA): 0.5093
• 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
E/A	None	None	0.565	N	0.546	0.195	0.264081493735	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
E/A	0.1268	likely_benign	0.1529	benign	-0.339	Destabilizing	0.565	D	0.546	neutral	N	0.475288172	None	None	N
E/C	0.731	likely_pathogenic	0.8093	pathogenic	-0.329	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	N
E/D	0.0755	likely_benign	0.0946	benign	-0.439	Destabilizing	0.003	N	0.097	neutral	N	0.442986539	None	None	N
E/F	0.6104	likely_pathogenic	0.7055	pathogenic	-0.056	Destabilizing	0.987	D	0.655	neutral	None	None	None	None	N
E/G	0.1399	likely_benign	0.1581	benign	-0.559	Destabilizing	0.565	D	0.557	neutral	N	0.479157983	None	None	N
E/H	0.3682	ambiguous	0.4332	ambiguous	0.304	Stabilizing	0.961	D	0.529	neutral	None	None	None	None	N
E/I	0.2708	likely_benign	0.3398	benign	0.217	Stabilizing	0.961	D	0.652	neutral	None	None	None	None	N
E/K	0.172	likely_benign	0.1768	benign	0.085	Stabilizing	0.722	D	0.499	neutral	N	0.462879022	None	None	N
E/L	0.311	likely_benign	0.3909	ambiguous	0.217	Stabilizing	0.961	D	0.589	neutral	None	None	None	None	N
E/M	0.3743	ambiguous	0.4345	ambiguous	0.103	Stabilizing	0.996	D	0.647	neutral	None	None	None	None	N
E/N	0.1452	likely_benign	0.1939	benign	-0.288	Destabilizing	0.011	N	0.228	neutral	None	None	None	None	N
E/P	0.7382	likely_pathogenic	0.7807	pathogenic	0.052	Stabilizing	0.961	D	0.606	neutral	None	None	None	None	N
E/Q	0.1368	likely_benign	0.1486	benign	-0.225	Destabilizing	0.722	D	0.504	neutral	N	0.444639978	None	None	N
E/R	0.2857	likely_benign	0.2962	benign	0.452	Stabilizing	0.923	D	0.515	neutral	None	None	None	None	N
E/S	0.146	likely_benign	0.1862	benign	-0.463	Destabilizing	0.118	N	0.228	neutral	None	None	None	None	N
E/T	0.1679	likely_benign	0.2031	benign	-0.282	Destabilizing	0.633	D	0.581	neutral	None	None	None	None	N
E/V	0.1711	likely_benign	0.2008	benign	0.052	Stabilizing	0.949	D	0.595	neutral	N	0.481427497	None	None	N
E/W	0.8594	likely_pathogenic	0.8936	pathogenic	0.114	Stabilizing	0.996	D	0.698	prob.neutral	None	None	None	None	N
E/Y	0.4725	ambiguous	0.5665	pathogenic	0.185	Stabilizing	0.987	D	0.648	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.