TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22509	67750;67751;67752	chr2:178579672;178579671;178579670	chr2:179444399;179444398;179444397
N2AB	20868	62827;62828;62829	chr2:178579672;178579671;178579670	chr2:179444399;179444398;179444397
N2A	19941	60046;60047;60048	chr2:178579672;178579671;178579670	chr2:179444399;179444398;179444397
N2B	13444	40555;40556;40557	chr2:178579672;178579671;178579670	chr2:179444399;179444398;179444397
Novex-1	13569	40930;40931;40932	chr2:178579672;178579671;178579670	chr2:179444399;179444398;179444397
Novex-2	13636	41131;41132;41133	chr2:178579672;178579671;178579670	chr2:179444399;179444398;179444397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-51
• Domain position: 59
• Structural Position: 92
• Q(SASA): 0.3922
• 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/P	None	None	0.484	N	0.547	0.214	0.235038932564	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	2.77778E-05	None	0	0	0	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
S/A	0.0798	likely_benign	0.0832	benign	-0.585	Destabilizing	0.012	N	0.273	neutral	N	0.470130281	None	None	N
S/C	0.0979	likely_benign	0.0988	benign	-0.372	Destabilizing	0.78	D	0.505	neutral	N	0.494065934	None	None	N
S/D	0.2735	likely_benign	0.2908	benign	0.152	Stabilizing	0.149	N	0.421	neutral	None	None	None	None	N
S/E	0.3096	likely_benign	0.3353	benign	0.111	Stabilizing	0.149	N	0.41	neutral	None	None	None	None	N
S/F	0.1421	likely_benign	0.1719	benign	-0.956	Destabilizing	None	N	0.43	neutral	N	0.512747695	None	None	N
S/G	0.1102	likely_benign	0.1094	benign	-0.777	Destabilizing	0.067	N	0.439	neutral	None	None	None	None	N
S/H	0.2174	likely_benign	0.2222	benign	-1.221	Destabilizing	0.791	D	0.516	neutral	None	None	None	None	N
S/I	0.1033	likely_benign	0.1104	benign	-0.195	Destabilizing	0.081	N	0.52	neutral	None	None	None	None	N
S/K	0.4648	ambiguous	0.5039	ambiguous	-0.574	Destabilizing	0.149	N	0.397	neutral	None	None	None	None	N
S/L	0.0783	likely_benign	0.0883	benign	-0.195	Destabilizing	0.035	N	0.461	neutral	None	None	None	None	N
S/M	0.1537	likely_benign	0.1561	benign	-0.017	Destabilizing	0.555	D	0.523	neutral	None	None	None	None	N
S/N	0.1158	likely_benign	0.1081	benign	-0.393	Destabilizing	0.149	N	0.449	neutral	None	None	None	None	N
S/P	0.2773	likely_benign	0.3727	ambiguous	-0.292	Destabilizing	0.484	N	0.547	neutral	N	0.489678834	None	None	N
S/Q	0.3366	likely_benign	0.343	ambiguous	-0.543	Destabilizing	0.555	D	0.514	neutral	None	None	None	None	N
S/R	0.3804	ambiguous	0.432	ambiguous	-0.433	Destabilizing	0.38	N	0.553	neutral	None	None	None	None	N
S/T	0.0611	likely_benign	0.0604	benign	-0.456	Destabilizing	None	N	0.145	neutral	N	0.353510967	None	None	N
S/V	0.1064	likely_benign	0.1104	benign	-0.292	Destabilizing	0.002	N	0.423	neutral	None	None	None	None	N
S/W	0.2669	likely_benign	0.3169	benign	-0.949	Destabilizing	0.935	D	0.595	neutral	None	None	None	None	N
S/Y	0.1448	likely_benign	0.1708	benign	-0.681	Destabilizing	0.188	N	0.599	neutral	N	0.504589572	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.