TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27865	83818;83819;83820	chr2:178562539;178562538;178562537	chr2:179427266;179427265;179427264
N2AB	26224	78895;78896;78897	chr2:178562539;178562538;178562537	chr2:179427266;179427265;179427264
N2A	25297	76114;76115;76116	chr2:178562539;178562538;178562537	chr2:179427266;179427265;179427264
N2B	18800	56623;56624;56625	chr2:178562539;178562538;178562537	chr2:179427266;179427265;179427264
Novex-1	18925	56998;56999;57000	chr2:178562539;178562538;178562537	chr2:179427266;179427265;179427264
Novex-2	18992	57199;57200;57201	chr2:178562539;178562538;178562537	chr2:179427266;179427265;179427264
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-91
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.4283
• 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
L/F	rs1267898928	-1.341	0.943	N	0.609	0.167	0.478828542108	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
L/F	rs1267898928	-1.341	0.943	N	0.609	0.167	0.478828542108	gnomAD-4.0.0	1.60041E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86809E-06	0	0
L/P	None	None	0.994	N	0.768	0.4	0.737259829814	gnomAD-4.0.0	6.85811E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00385E-07	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
L/A	0.1331	likely_benign	0.131	benign	-1.576	Destabilizing	0.94	D	0.497	neutral	None	None	None	None	N
L/C	0.3739	ambiguous	0.3608	ambiguous	-0.891	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
L/D	0.5283	ambiguous	0.5409	ambiguous	-1.031	Destabilizing	0.991	D	0.76	deleterious	None	None	None	None	N
L/E	0.2926	likely_benign	0.3071	benign	-1.062	Destabilizing	0.988	D	0.747	deleterious	None	None	None	None	N
L/F	0.1215	likely_benign	0.1142	benign	-1.259	Destabilizing	0.943	D	0.609	neutral	N	0.474541428	None	None	N
L/G	0.2731	likely_benign	0.2604	benign	-1.863	Destabilizing	0.982	D	0.675	neutral	None	None	None	None	N
L/H	0.1831	likely_benign	0.172	benign	-1.096	Destabilizing	0.992	D	0.757	deleterious	N	0.474287938	None	None	N
L/I	0.1545	likely_benign	0.1536	benign	-0.876	Destabilizing	0.41	N	0.504	neutral	N	0.463185122	None	None	N
L/K	0.2529	likely_benign	0.2767	benign	-0.955	Destabilizing	0.763	D	0.657	neutral	None	None	None	None	N
L/M	0.0999	likely_benign	0.1004	benign	-0.6	Destabilizing	0.988	D	0.643	neutral	None	None	None	None	N
L/N	0.2315	likely_benign	0.2074	benign	-0.708	Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	N
L/P	0.707	likely_pathogenic	0.7269	pathogenic	-1.077	Destabilizing	0.994	D	0.768	deleterious	N	0.47302049	None	None	N
L/Q	0.1032	likely_benign	0.1026	benign	-0.955	Destabilizing	0.989	D	0.749	deleterious	None	None	None	None	N
L/R	0.2221	likely_benign	0.2443	benign	-0.332	Destabilizing	0.971	D	0.745	deleterious	N	0.462424654	None	None	N
L/S	0.106	likely_benign	0.0993	benign	-1.298	Destabilizing	0.492	N	0.419	neutral	None	None	None	None	N
L/T	0.1573	likely_benign	0.1531	benign	-1.22	Destabilizing	0.825	D	0.631	neutral	None	None	None	None	N
L/V	0.1172	likely_benign	0.1203	benign	-1.077	Destabilizing	0.477	N	0.49	neutral	N	0.505970864	None	None	N
L/W	0.3072	likely_benign	0.2951	benign	-1.287	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/Y	0.2416	likely_benign	0.2213	benign	-1.061	Destabilizing	0.01	N	0.367	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.