TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23504	70735;70736;70737	chr2:178575622;178575621;178575620	chr2:179440349;179440348;179440347
N2AB	21863	65812;65813;65814	chr2:178575622;178575621;178575620	chr2:179440349;179440348;179440347
N2A	20936	63031;63032;63033	chr2:178575622;178575621;178575620	chr2:179440349;179440348;179440347
N2B	14439	43540;43541;43542	chr2:178575622;178575621;178575620	chr2:179440349;179440348;179440347
Novex-1	14564	43915;43916;43917	chr2:178575622;178575621;178575620	chr2:179440349;179440348;179440347
Novex-2	14631	44116;44117;44118	chr2:178575622;178575621;178575620	chr2:179440349;179440348;179440347
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: Fn3-58
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.4532
• 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	None	N	0.109	0.083	0.240491677333	gnomAD-4.0.0	6.84291E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99557E-07	0	0
E/Q	rs1362847983	-0.858	0.002	N	0.199	0.116	0.275641507738	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	9.19118E-04
E/Q	rs1362847983	-0.858	0.002	N	0.199	0.116	0.275641507738	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/Q	rs1362847983	-0.858	0.002	N	0.199	0.116	0.275641507738	gnomAD-4.0.0	5.07505E-06	None	None	None	None	N	None	0	6.15612E-05	None	0	0	None	0	0	3.61491E-06	0	3.40298E-05

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	0.1943	likely_benign	0.2083	benign	-0.951	Destabilizing	0.117	N	0.443	neutral	N	0.498261032	None	None	N
E/C	0.8175	likely_pathogenic	0.8235	pathogenic	-0.568	Destabilizing	0.935	D	0.635	neutral	None	None	None	None	N
E/D	0.1413	likely_benign	0.1845	benign	-1.189	Destabilizing	None	N	0.109	neutral	N	0.502493416	None	None	N
E/F	0.781	likely_pathogenic	0.8045	pathogenic	-0.261	Destabilizing	0.235	N	0.591	neutral	None	None	None	None	N
E/G	0.283	likely_benign	0.3149	benign	-1.35	Destabilizing	0.117	N	0.516	neutral	N	0.517366868	None	None	N
E/H	0.5587	ambiguous	0.5918	pathogenic	-0.588	Destabilizing	0.38	N	0.517	neutral	None	None	None	None	N
E/I	0.3956	ambiguous	0.4505	ambiguous	0.15	Stabilizing	0.555	D	0.612	neutral	None	None	None	None	N
E/K	0.3272	likely_benign	0.3711	ambiguous	-0.908	Destabilizing	0.062	N	0.388	neutral	N	0.496066089	None	None	N
E/L	0.4354	ambiguous	0.4482	ambiguous	0.15	Stabilizing	0.149	N	0.565	neutral	None	None	None	None	N
E/M	0.4939	ambiguous	0.5074	ambiguous	0.654	Stabilizing	0.824	D	0.597	neutral	None	None	None	None	N
E/N	0.2916	likely_benign	0.352	ambiguous	-1.368	Destabilizing	0.081	N	0.451	neutral	None	None	None	None	N
E/P	0.5963	likely_pathogenic	0.6319	pathogenic	-0.196	Destabilizing	0.555	D	0.565	neutral	None	None	None	None	N
E/Q	0.1869	likely_benign	0.1896	benign	-1.195	Destabilizing	0.002	N	0.199	neutral	N	0.463359025	None	None	N
E/R	0.4526	ambiguous	0.4947	ambiguous	-0.584	Destabilizing	0.235	N	0.479	neutral	None	None	None	None	N
E/S	0.1912	likely_benign	0.2085	benign	-1.738	Destabilizing	0.081	N	0.373	neutral	None	None	None	None	N
E/T	0.2435	likely_benign	0.2672	benign	-1.408	Destabilizing	0.149	N	0.519	neutral	None	None	None	None	N
E/V	0.258	likely_benign	0.2908	benign	-0.196	Destabilizing	0.117	N	0.571	neutral	N	0.500839977	None	None	N
E/W	0.9251	likely_pathogenic	0.934	pathogenic	-0.006	Destabilizing	0.935	D	0.609	neutral	None	None	None	None	N
E/Y	0.6343	likely_pathogenic	0.6785	pathogenic	-0.022	Destabilizing	0.002	N	0.299	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.