TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26543	79852;79853;79854	chr2:178566505;178566504;178566503	chr2:179431232;179431231;179431230
N2AB	24902	74929;74930;74931	chr2:178566505;178566504;178566503	chr2:179431232;179431231;179431230
N2A	23975	72148;72149;72150	chr2:178566505;178566504;178566503	chr2:179431232;179431231;179431230
N2B	17478	52657;52658;52659	chr2:178566505;178566504;178566503	chr2:179431232;179431231;179431230
Novex-1	17603	53032;53033;53034	chr2:178566505;178566504;178566503	chr2:179431232;179431231;179431230
Novex-2	17670	53233;53234;53235	chr2:178566505;178566504;178566503	chr2:179431232;179431231;179431230
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-81
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.0566
• 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/P	rs1237559508	-1.677	0.995	D	0.785	0.508	0.790206724357	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/P	rs1237559508	-1.677	0.995	D	0.785	0.508	0.790206724357	gnomAD-4.0.0	3.18385E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71775E-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
L/A	0.4639	ambiguous	0.5251	ambiguous	-1.917	Destabilizing	0.825	D	0.616	neutral	None	None	None	None	N
L/C	0.5125	ambiguous	0.5741	pathogenic	-1.15	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
L/D	0.8888	likely_pathogenic	0.9173	pathogenic	-1.97	Destabilizing	0.996	D	0.786	deleterious	None	None	None	None	N
L/E	0.6114	likely_pathogenic	0.6499	pathogenic	-1.691	Destabilizing	0.996	D	0.78	deleterious	None	None	None	None	N
L/F	0.2028	likely_benign	0.2263	benign	-0.992	Destabilizing	0.976	D	0.688	prob.neutral	None	None	None	None	N
L/G	0.7239	likely_pathogenic	0.7944	pathogenic	-2.504	Highly Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	N
L/H	0.4088	ambiguous	0.446	ambiguous	-2.138	Highly Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
L/I	0.0878	likely_benign	0.093	benign	-0.211	Destabilizing	0.015	N	0.228	neutral	None	None	None	None	N
L/K	0.4846	ambiguous	0.5231	ambiguous	-1.165	Destabilizing	0.988	D	0.715	prob.delet.	None	None	None	None	N
L/M	0.1437	likely_benign	0.1524	benign	-0.339	Destabilizing	0.968	D	0.701	prob.neutral	N	0.495006448	None	None	N
L/N	0.5971	likely_pathogenic	0.6549	pathogenic	-1.619	Destabilizing	0.996	D	0.796	deleterious	None	None	None	None	N
L/P	0.762	likely_pathogenic	0.8186	pathogenic	-0.761	Destabilizing	0.995	D	0.785	deleterious	D	0.523231261	None	None	N
L/Q	0.2851	likely_benign	0.3162	benign	-1.34	Destabilizing	0.995	D	0.739	prob.delet.	N	0.480002838	None	None	N
L/R	0.4179	ambiguous	0.4582	ambiguous	-1.253	Destabilizing	0.995	D	0.723	prob.delet.	N	0.485163718	None	None	N
L/S	0.534	ambiguous	0.59	pathogenic	-2.336	Highly Destabilizing	0.988	D	0.703	prob.neutral	None	None	None	None	N
L/T	0.4175	ambiguous	0.4699	ambiguous	-1.89	Destabilizing	0.919	D	0.683	prob.neutral	None	None	None	None	N
L/V	0.1019	likely_benign	0.1128	benign	-0.761	Destabilizing	0.046	N	0.257	neutral	N	0.430958605	None	None	N
L/W	0.4072	ambiguous	0.4448	ambiguous	-1.387	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	N
L/Y	0.4961	ambiguous	0.5461	ambiguous	-1.011	Destabilizing	0.996	D	0.728	prob.delet.	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.