TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28999	87220;87221;87222	chr2:178558464;178558463;178558462	chr2:179423191;179423190;179423189
N2AB	27358	82297;82298;82299	chr2:178558464;178558463;178558462	chr2:179423191;179423190;179423189
N2A	26431	79516;79517;79518	chr2:178558464;178558463;178558462	chr2:179423191;179423190;179423189
N2B	19934	60025;60026;60027	chr2:178558464;178558463;178558462	chr2:179423191;179423190;179423189
Novex-1	20059	60400;60401;60402	chr2:178558464;178558463;178558462	chr2:179423191;179423190;179423189
Novex-2	20126	60601;60602;60603	chr2:178558464;178558463;178558462	chr2:179423191;179423190;179423189
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-99
• Domain position: 58
• Structural Position: 90
• Q(SASA): 0.5922
• 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
H/D	rs879148150	None	0.062	N	0.409	0.259	None	gnomAD-4.0.0	1.36842E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79888E-06	0	0
H/Y	rs879148150	None	0.211	N	0.448	0.195	0.261217442401	gnomAD-4.0.0	1.36842E-06	None	None	None	None	I	None	2.98721E-05	0	None	0	0	None	0	0	8.99441E-07	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
H/A	0.1497	likely_benign	0.1576	benign	-0.378	Destabilizing	0.081	N	0.464	neutral	None	None	None	None	I
H/C	0.1046	likely_benign	0.1152	benign	0.491	Stabilizing	0.935	D	0.607	neutral	None	None	None	None	I
H/D	0.1536	likely_benign	0.1576	benign	-0.216	Destabilizing	0.062	N	0.409	neutral	N	0.459009211	None	None	I
H/E	0.1617	likely_benign	0.1602	benign	-0.13	Destabilizing	0.035	N	0.393	neutral	None	None	None	None	I
H/F	0.1912	likely_benign	0.1907	benign	0.729	Stabilizing	0.555	D	0.533	neutral	None	None	None	None	I
H/G	0.1901	likely_benign	0.2162	benign	-0.742	Destabilizing	0.081	N	0.46	neutral	None	None	None	None	I
H/I	0.1686	likely_benign	0.1709	benign	0.61	Stabilizing	0.555	D	0.574	neutral	None	None	None	None	I
H/K	0.1617	likely_benign	0.1804	benign	-0.168	Destabilizing	0.081	N	0.393	neutral	None	None	None	None	I
H/L	0.1002	likely_benign	0.1059	benign	0.61	Stabilizing	0.117	N	0.511	neutral	N	0.485945096	None	None	I
H/M	0.2957	likely_benign	0.3029	benign	0.472	Stabilizing	0.824	D	0.565	neutral	None	None	None	None	I
H/N	0.0782	likely_benign	0.0797	benign	-0.206	Destabilizing	None	N	0.247	neutral	N	0.424741921	None	None	I
H/P	0.4931	ambiguous	0.6145	pathogenic	0.303	Stabilizing	0.484	N	0.563	neutral	N	0.504357498	None	None	I
H/Q	0.0977	likely_benign	0.1028	benign	0.013	Stabilizing	None	N	0.367	neutral	N	0.449618936	None	None	I
H/R	0.0796	likely_benign	0.0897	benign	-0.764	Destabilizing	None	N	0.337	neutral	N	0.4169678	None	None	I
H/S	0.1071	likely_benign	0.1081	benign	-0.187	Destabilizing	0.081	N	0.398	neutral	None	None	None	None	I
H/T	0.1124	likely_benign	0.1102	benign	0.003	Stabilizing	0.149	N	0.519	neutral	None	None	None	None	I
H/V	0.1315	likely_benign	0.1338	benign	0.303	Stabilizing	0.38	N	0.557	neutral	None	None	None	None	I
H/W	0.3011	likely_benign	0.3145	benign	0.941	Stabilizing	0.935	D	0.602	neutral	None	None	None	None	I
H/Y	0.0835	likely_benign	0.0799	benign	1.086	Stabilizing	0.211	N	0.448	neutral	N	0.476786895	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.