TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19921	59986;59987;59988	chr2:178592143;178592142;178592141	chr2:179456870;179456869;179456868
N2AB	18280	55063;55064;55065	chr2:178592143;178592142;178592141	chr2:179456870;179456869;179456868
N2A	17353	52282;52283;52284	chr2:178592143;178592142;178592141	chr2:179456870;179456869;179456868
N2B	10856	32791;32792;32793	chr2:178592143;178592142;178592141	chr2:179456870;179456869;179456868
Novex-1	10981	33166;33167;33168	chr2:178592143;178592142;178592141	chr2:179456870;179456869;179456868
Novex-2	11048	33367;33368;33369	chr2:178592143;178592142;178592141	chr2:179456870;179456869;179456868
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-32
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.2716
• 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
S/T	rs749120617	-0.343	None	N	0.121	0.124	0.0884992946249	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	3.27E-05	None	0	0	0
S/T	rs749120617	-0.343	None	N	0.121	0.124	0.0884992946249	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
S/T	rs749120617	-0.343	None	N	0.121	0.124	0.0884992946249	gnomAD-4.0.0	2.4802E-06	None	None	None	None	N	None	4.00812E-05	0	None	0	0	None	0	0	0	1.09837E-05	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
S/A	0.0688	likely_benign	0.0672	benign	-0.337	Destabilizing	0.002	N	0.155	neutral	None	None	None	None	N
S/C	0.1245	likely_benign	0.1093	benign	-0.296	Destabilizing	0.78	D	0.274	neutral	N	0.514417831	None	None	N
S/D	0.3375	likely_benign	0.3075	benign	-0.104	Destabilizing	0.081	N	0.287	neutral	None	None	None	None	N
S/E	0.4142	ambiguous	0.3991	ambiguous	-0.212	Destabilizing	0.149	N	0.304	neutral	None	None	None	None	N
S/F	0.1923	likely_benign	0.2085	benign	-0.956	Destabilizing	0.555	D	0.343	neutral	None	None	None	None	N
S/G	0.0888	likely_benign	0.064	benign	-0.426	Destabilizing	None	N	0.141	neutral	N	0.50624301	None	None	N
S/H	0.2754	likely_benign	0.2752	benign	-0.897	Destabilizing	0.824	D	0.262	neutral	None	None	None	None	N
S/I	0.1736	likely_benign	0.1685	benign	-0.234	Destabilizing	0.188	N	0.362	neutral	N	0.514164341	None	None	N
S/K	0.454	ambiguous	0.4472	ambiguous	-0.551	Destabilizing	0.149	N	0.321	neutral	None	None	None	None	N
S/L	0.0885	likely_benign	0.0919	benign	-0.234	Destabilizing	0.081	N	0.312	neutral	None	None	None	None	N
S/M	0.149	likely_benign	0.1316	benign	0.044	Stabilizing	0.824	D	0.259	neutral	None	None	None	None	N
S/N	0.1132	likely_benign	0.0984	benign	-0.251	Destabilizing	None	N	0.201	neutral	N	0.499087751	None	None	N
S/P	0.6285	likely_pathogenic	0.5913	pathogenic	-0.241	Destabilizing	0.555	D	0.293	neutral	None	None	None	None	N
S/Q	0.3673	ambiguous	0.3521	ambiguous	-0.553	Destabilizing	0.555	D	0.297	neutral	None	None	None	None	N
S/R	0.4117	ambiguous	0.4094	ambiguous	-0.263	Destabilizing	0.541	D	0.301	neutral	N	0.474384095	None	None	N
S/T	0.0717	likely_benign	0.0648	benign	-0.363	Destabilizing	None	N	0.121	neutral	N	0.47926984	None	None	N
S/V	0.146	likely_benign	0.1358	benign	-0.241	Destabilizing	0.081	N	0.352	neutral	None	None	None	None	N
S/W	0.3489	ambiguous	0.3453	ambiguous	-0.964	Destabilizing	0.935	D	0.496	neutral	None	None	None	None	N
S/Y	0.1884	likely_benign	0.2011	benign	-0.694	Destabilizing	0.555	D	0.341	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.