TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28577	85954;85955;85956	chr2:178560403;178560402;178560401	chr2:179425130;179425129;179425128
N2AB	26936	81031;81032;81033	chr2:178560403;178560402;178560401	chr2:179425130;179425129;179425128
N2A	26009	78250;78251;78252	chr2:178560403;178560402;178560401	chr2:179425130;179425129;179425128
N2B	19512	58759;58760;58761	chr2:178560403;178560402;178560401	chr2:179425130;179425129;179425128
Novex-1	19637	59134;59135;59136	chr2:178560403;178560402;178560401	chr2:179425130;179425129;179425128
Novex-2	19704	59335;59336;59337	chr2:178560403;178560402;178560401	chr2:179425130;179425129;179425128
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-96
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2923
• Predicted PPI site: I

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
D/E	None	None	1.0	N	0.448	0.314	0.388010793773	gnomAD-4.0.0	1.36851E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31879E-05	0
D/N	None	None	1.0	N	0.696	0.361	0.394230963961	gnomAD-4.0.0	1.5915E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85817E-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
D/A	0.6124	likely_pathogenic	0.6447	pathogenic	-0.408	Destabilizing	1.0	D	0.719	prob.delet.	N	0.504085029	None	None	I
D/C	0.8938	likely_pathogenic	0.9052	pathogenic	0.145	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	I
D/E	0.7255	likely_pathogenic	0.7402	pathogenic	-0.595	Destabilizing	1.0	D	0.448	neutral	N	0.49945022	None	None	I
D/F	0.9389	likely_pathogenic	0.9499	pathogenic	-0.768	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
D/G	0.5886	likely_pathogenic	0.6122	pathogenic	-0.621	Destabilizing	1.0	D	0.7	prob.neutral	N	0.503630956	None	None	I
D/H	0.7371	likely_pathogenic	0.766	pathogenic	-1.058	Destabilizing	1.0	D	0.65	neutral	N	0.507149675	None	None	I
D/I	0.8568	likely_pathogenic	0.8848	pathogenic	0.11	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
D/K	0.8754	likely_pathogenic	0.8927	pathogenic	0.183	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
D/L	0.8617	likely_pathogenic	0.8775	pathogenic	0.11	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
D/M	0.9295	likely_pathogenic	0.9407	pathogenic	0.6	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	I
D/N	0.1279	likely_benign	0.1344	benign	-0.064	Destabilizing	1.0	D	0.696	prob.neutral	N	0.519540381	None	None	I
D/P	0.9396	likely_pathogenic	0.9414	pathogenic	-0.041	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
D/Q	0.8576	likely_pathogenic	0.875	pathogenic	-0.042	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
D/R	0.8618	likely_pathogenic	0.8814	pathogenic	0.023	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
D/S	0.2532	likely_benign	0.2825	benign	-0.188	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
D/T	0.4402	ambiguous	0.5083	ambiguous	-0.012	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
D/V	0.7119	likely_pathogenic	0.7601	pathogenic	-0.041	Destabilizing	1.0	D	0.699	prob.neutral	N	0.515859408	None	None	I
D/W	0.9861	likely_pathogenic	0.9881	pathogenic	-0.762	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
D/Y	0.6755	likely_pathogenic	0.7177	pathogenic	-0.555	Destabilizing	1.0	D	0.628	neutral	D	0.551360356	None	None	I

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.