TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29955	90088;90089;90090	chr2:178553037;178553036;178553035	chr2:179417764;179417763;179417762
N2AB	28314	85165;85166;85167	chr2:178553037;178553036;178553035	chr2:179417764;179417763;179417762
N2A	27387	82384;82385;82386	chr2:178553037;178553036;178553035	chr2:179417764;179417763;179417762
N2B	20890	62893;62894;62895	chr2:178553037;178553036;178553035	chr2:179417764;179417763;179417762
Novex-1	21015	63268;63269;63270	chr2:178553037;178553036;178553035	chr2:179417764;179417763;179417762
Novex-2	21082	63469;63470;63471	chr2:178553037;178553036;178553035	chr2:179417764;179417763;179417762
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: Fn3-106
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.2797
• 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
D/N	rs1700018329	None	0.117	N	0.44	0.205	0.184867976434	gnomAD-4.0.0	1.37014E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79903E-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	0.17	likely_benign	0.1718	benign	-0.554	Destabilizing	0.062	N	0.535	neutral	N	0.508533954	None	None	N
D/C	0.594	likely_pathogenic	0.5933	pathogenic	-0.438	Destabilizing	0.935	D	0.643	neutral	None	None	None	None	N
D/E	0.074	likely_benign	0.0767	benign	-0.826	Destabilizing	None	N	0.121	neutral	N	0.40940711	None	None	N
D/F	0.555	ambiguous	0.5493	ambiguous	-0.239	Destabilizing	0.791	D	0.607	neutral	None	None	None	None	N
D/G	0.2426	likely_benign	0.2599	benign	-0.902	Destabilizing	0.117	N	0.475	neutral	N	0.468192461	None	None	N
D/H	0.2993	likely_benign	0.2991	benign	-0.713	Destabilizing	0.484	N	0.521	neutral	N	0.488107141	None	None	N
D/I	0.2831	likely_benign	0.2867	benign	0.367	Stabilizing	0.555	D	0.615	neutral	None	None	None	None	N
D/K	0.3456	ambiguous	0.373	ambiguous	-0.996	Destabilizing	0.081	N	0.497	neutral	None	None	None	None	N
D/L	0.2838	likely_benign	0.2776	benign	0.367	Stabilizing	0.38	N	0.597	neutral	None	None	None	None	N
D/M	0.4314	ambiguous	0.4238	ambiguous	0.791	Stabilizing	0.935	D	0.597	neutral	None	None	None	None	N
D/N	0.117	likely_benign	0.1111	benign	-1.215	Destabilizing	0.117	N	0.44	neutral	N	0.476768252	None	None	N
D/P	0.9252	likely_pathogenic	0.9433	pathogenic	0.085	Stabilizing	0.555	D	0.529	neutral	None	None	None	None	N
D/Q	0.2357	likely_benign	0.2371	benign	-1.049	Destabilizing	0.081	N	0.416	neutral	None	None	None	None	N
D/R	0.4578	ambiguous	0.4961	ambiguous	-0.798	Destabilizing	0.235	N	0.599	neutral	None	None	None	None	N
D/S	0.1357	likely_benign	0.1322	benign	-1.499	Destabilizing	0.081	N	0.465	neutral	None	None	None	None	N
D/T	0.2114	likely_benign	0.2133	benign	-1.233	Destabilizing	0.149	N	0.495	neutral	None	None	None	None	N
D/V	0.1751	likely_benign	0.1796	benign	0.085	Stabilizing	0.317	N	0.595	neutral	N	0.520463101	None	None	N
D/W	0.8688	likely_pathogenic	0.8784	pathogenic	-0.184	Destabilizing	0.935	D	0.658	neutral	None	None	None	None	N
D/Y	0.2342	likely_benign	0.233	benign	-0.089	Destabilizing	0.741	D	0.61	neutral	N	0.46844595	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.