TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6897	20914;20915;20916	chr2:178725515;178725514;178725513	chr2:179590242;179590241;179590240
N2AB	6580	19963;19964;19965	chr2:178725515;178725514;178725513	chr2:179590242;179590241;179590240
N2A	5653	17182;17183;17184	chr2:178725515;178725514;178725513	chr2:179590242;179590241;179590240
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-53
• Domain position: 44
• Structural Position: 70
• Q(SASA): 0.6151
• 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/D	None	None	0.031	N	0.16	0.062	0.177238962908	gnomAD-4.0.0	1.36881E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79934E-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	0.254	likely_benign	0.2452	benign	-0.38	Destabilizing	0.961	D	0.463	neutral	D	0.534059622	None	None	N
E/C	0.9608	likely_pathogenic	0.9656	pathogenic	-0.255	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	N
E/D	0.2739	likely_benign	0.268	benign	-0.475	Destabilizing	0.031	N	0.16	neutral	N	0.481420002	None	None	N
E/F	0.8955	likely_pathogenic	0.9247	pathogenic	0.032	Stabilizing	0.999	D	0.543	neutral	None	None	None	None	N
E/G	0.2652	likely_benign	0.2899	benign	-0.626	Destabilizing	0.961	D	0.463	neutral	N	0.493685408	None	None	N
E/H	0.8043	likely_pathogenic	0.82	pathogenic	0.332	Stabilizing	0.999	D	0.407	neutral	None	None	None	None	N
E/I	0.6879	likely_pathogenic	0.6872	pathogenic	0.251	Stabilizing	0.999	D	0.539	neutral	None	None	None	None	N
E/K	0.3659	ambiguous	0.3891	ambiguous	0.275	Stabilizing	0.248	N	0.176	neutral	N	0.494379744	None	None	N
E/L	0.6827	likely_pathogenic	0.6983	pathogenic	0.251	Stabilizing	0.996	D	0.459	neutral	None	None	None	None	N
E/M	0.7533	likely_pathogenic	0.7648	pathogenic	0.211	Stabilizing	1.0	D	0.524	neutral	None	None	None	None	N
E/N	0.5048	ambiguous	0.5134	ambiguous	-0.327	Destabilizing	0.97	D	0.423	neutral	None	None	None	None	N
E/P	0.4895	ambiguous	0.4572	ambiguous	0.062	Stabilizing	0.999	D	0.433	neutral	None	None	None	None	N
E/Q	0.2819	likely_benign	0.2838	benign	-0.226	Destabilizing	0.961	D	0.435	neutral	N	0.494379744	None	None	N
E/R	0.5759	likely_pathogenic	0.6131	pathogenic	0.596	Stabilizing	0.942	D	0.405	neutral	None	None	None	None	N
E/S	0.4015	ambiguous	0.4024	ambiguous	-0.451	Destabilizing	0.97	D	0.433	neutral	None	None	None	None	N
E/T	0.489	ambiguous	0.4849	ambiguous	-0.234	Destabilizing	0.985	D	0.457	neutral	None	None	None	None	N
E/V	0.453	ambiguous	0.4535	ambiguous	0.062	Stabilizing	0.994	D	0.435	neutral	N	0.50264863	None	None	N
E/W	0.9659	likely_pathogenic	0.9774	pathogenic	0.26	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
E/Y	0.8311	likely_pathogenic	0.8665	pathogenic	0.297	Stabilizing	0.999	D	0.517	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.