TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31149	93670;93671;93672	chr2:178548181;178548180;178548179	chr2:179412908;179412907;179412906
N2AB	29508	88747;88748;88749	chr2:178548181;178548180;178548179	chr2:179412908;179412907;179412906
N2A	28581	85966;85967;85968	chr2:178548181;178548180;178548179	chr2:179412908;179412907;179412906
N2B	22084	66475;66476;66477	chr2:178548181;178548180;178548179	chr2:179412908;179412907;179412906
Novex-1	22209	66850;66851;66852	chr2:178548181;178548180;178548179	chr2:179412908;179412907;179412906
Novex-2	22276	67051;67052;67053	chr2:178548181;178548180;178548179	chr2:179412908;179412907;179412906
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: Fn3-115
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1947
• 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/V	None	None	0.248	N	0.377	0.063	0.424073947737	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2297	likely_benign	0.2516	benign	-2.719	Highly Destabilizing	0.97	D	0.686	prob.neutral	None	None	None	None	N
L/C	0.2863	likely_benign	0.2899	benign	-1.847	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
L/D	0.6587	likely_pathogenic	0.7076	pathogenic	-3.188	Highly Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
L/E	0.3376	likely_benign	0.3496	ambiguous	-2.984	Highly Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
L/F	0.1131	likely_benign	0.1223	benign	-1.651	Destabilizing	0.996	D	0.726	prob.delet.	None	None	None	None	N
L/G	0.5675	likely_pathogenic	0.6116	pathogenic	-3.225	Highly Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	N
L/H	0.1433	likely_benign	0.1441	benign	-2.681	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/I	0.0654	likely_benign	0.0677	benign	-1.251	Destabilizing	0.155	N	0.299	neutral	None	None	None	None	N
L/K	0.2394	likely_benign	0.2568	benign	-2.112	Highly Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
L/M	0.1008	likely_benign	0.1033	benign	-1.117	Destabilizing	0.994	D	0.721	prob.delet.	N	0.502685417	None	None	N
L/N	0.3673	ambiguous	0.4358	ambiguous	-2.405	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
L/P	0.9706	likely_pathogenic	0.9697	pathogenic	-1.724	Destabilizing	0.998	D	0.781	deleterious	N	0.492043934	None	None	N
L/Q	0.1252	likely_benign	0.1241	benign	-2.309	Highly Destabilizing	0.998	D	0.73	prob.delet.	N	0.484790303	None	None	N
L/R	0.1629	likely_benign	0.1551	benign	-1.724	Destabilizing	0.998	D	0.726	prob.delet.	N	0.464182957	None	None	N
L/S	0.2537	likely_benign	0.2839	benign	-3.031	Highly Destabilizing	0.996	D	0.7	prob.neutral	None	None	None	None	N
L/T	0.1792	likely_benign	0.1969	benign	-2.702	Highly Destabilizing	0.97	D	0.71	prob.delet.	None	None	None	None	N
L/V	0.0665	likely_benign	0.0663	benign	-1.724	Destabilizing	0.248	N	0.377	neutral	N	0.389591985	None	None	N
L/W	0.2497	likely_benign	0.2303	benign	-2.096	Highly Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
L/Y	0.2562	likely_benign	0.271	benign	-1.848	Destabilizing	0.999	D	0.723	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.