TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26920	80983;80984;80985	chr2:178565374;178565373;178565372	chr2:179430101;179430100;179430099
N2AB	25279	76060;76061;76062	chr2:178565374;178565373;178565372	chr2:179430101;179430100;179430099
N2A	24352	73279;73280;73281	chr2:178565374;178565373;178565372	chr2:179430101;179430100;179430099
N2B	17855	53788;53789;53790	chr2:178565374;178565373;178565372	chr2:179430101;179430100;179430099
Novex-1	17980	54163;54164;54165	chr2:178565374;178565373;178565372	chr2:179430101;179430100;179430099
Novex-2	18047	54364;54365;54366	chr2:178565374;178565373;178565372	chr2:179430101;179430100;179430099
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-139
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.264
• 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/H	None	None	0.883	D	0.716	0.766	0.880019082168	gnomAD-4.0.0	2.73712E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59822E-06	0	0
L/V	rs368431158	-1.517	0.001	D	0.285	0.197	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/V	rs368431158	-1.517	0.001	D	0.285	0.197	None	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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	0.8724	likely_pathogenic	0.8729	pathogenic	-2.368	Highly Destabilizing	0.157	N	0.507	neutral	None	None	None	None	N
L/C	0.8668	likely_pathogenic	0.8644	pathogenic	-1.494	Destabilizing	0.968	D	0.587	neutral	None	None	None	None	N
L/D	0.9977	likely_pathogenic	0.9971	pathogenic	-2.662	Highly Destabilizing	0.89	D	0.721	prob.delet.	None	None	None	None	N
L/E	0.9774	likely_pathogenic	0.9753	pathogenic	-2.462	Highly Destabilizing	0.726	D	0.713	prob.delet.	None	None	None	None	N
L/F	0.5076	ambiguous	0.4233	ambiguous	-1.454	Destabilizing	0.002	N	0.317	neutral	D	0.522179052	None	None	N
L/G	0.9812	likely_pathogenic	0.9784	pathogenic	-2.868	Highly Destabilizing	0.726	D	0.695	prob.neutral	None	None	None	None	N
L/H	0.9498	likely_pathogenic	0.9421	pathogenic	-2.278	Highly Destabilizing	0.883	D	0.716	prob.delet.	D	0.561047362	None	None	N
L/I	0.1339	likely_benign	0.1301	benign	-0.935	Destabilizing	0.001	N	0.214	neutral	N	0.516746084	None	None	N
L/K	0.9588	likely_pathogenic	0.9579	pathogenic	-1.897	Destabilizing	0.726	D	0.667	neutral	None	None	None	None	N
L/M	0.2649	likely_benign	0.2472	benign	-0.749	Destabilizing	0.567	D	0.525	neutral	None	None	None	None	N
L/N	0.9854	likely_pathogenic	0.9829	pathogenic	-2.12	Highly Destabilizing	0.89	D	0.72	prob.delet.	None	None	None	None	N
L/P	0.9539	likely_pathogenic	0.9542	pathogenic	-1.392	Destabilizing	0.859	D	0.723	prob.delet.	D	0.549437567	None	None	N
L/Q	0.8999	likely_pathogenic	0.8969	pathogenic	-2.039	Highly Destabilizing	0.89	D	0.679	prob.neutral	None	None	None	None	N
L/R	0.9259	likely_pathogenic	0.924	pathogenic	-1.576	Destabilizing	0.667	D	0.683	prob.neutral	D	0.554210507	None	None	N
L/S	0.9657	likely_pathogenic	0.961	pathogenic	-2.75	Highly Destabilizing	0.726	D	0.649	neutral	None	None	None	None	N
L/T	0.8836	likely_pathogenic	0.8883	pathogenic	-2.41	Highly Destabilizing	0.567	D	0.555	neutral	None	None	None	None	N
L/V	0.1414	likely_benign	0.1496	benign	-1.392	Destabilizing	0.001	N	0.285	neutral	D	0.525136281	None	None	N
L/W	0.8594	likely_pathogenic	0.821	pathogenic	-1.808	Destabilizing	0.909	D	0.7	prob.neutral	None	None	None	None	N
L/Y	0.9082	likely_pathogenic	0.877	pathogenic	-1.506	Destabilizing	0.396	N	0.594	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.