TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6250	18973;18974;18975	chr2:178729408;178729407;178729406	chr2:179594135;179594134;179594133
N2AB	5933	18022;18023;18024	chr2:178729408;178729407;178729406	chr2:179594135;179594134;179594133
N2A	5006	15241;15242;15243	chr2:178729408;178729407;178729406	chr2:179594135;179594134;179594133
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-46
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.5539
• 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
R/K	rs952849958	-0.342	None	N	0.135	0.15	0.159798565429	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
R/K	rs952849958	-0.342	None	N	0.135	0.15	0.159798565429	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/K	rs952849958	-0.342	None	N	0.135	0.15	0.159798565429	gnomAD-4.0.0	4.95807E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08616E-06	2.19563E-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
R/A	0.1298	likely_benign	0.1423	benign	-0.158	Destabilizing	0.016	N	0.315	neutral	None	None	None	None	N
R/C	0.1477	likely_benign	0.1764	benign	-0.155	Destabilizing	0.864	D	0.203	neutral	None	None	None	None	N
R/D	0.2016	likely_benign	0.2353	benign	0.024	Stabilizing	0.038	N	0.317	neutral	None	None	None	None	N
R/E	0.1332	likely_benign	0.1467	benign	0.095	Stabilizing	0.016	N	0.245	neutral	None	None	None	None	N
R/F	0.2805	likely_benign	0.3102	benign	-0.317	Destabilizing	0.12	N	0.281	neutral	None	None	None	None	N
R/G	0.0872	likely_benign	0.0919	benign	-0.38	Destabilizing	0.024	N	0.3	neutral	N	0.433242053	None	None	N
R/H	0.0769	likely_benign	0.0835	benign	-0.832	Destabilizing	None	N	0.158	neutral	None	None	None	None	N
R/I	0.1227	likely_benign	0.1344	benign	0.401	Stabilizing	0.295	N	0.273	neutral	N	0.423987852	None	None	N
R/K	0.0682	likely_benign	0.0752	benign	-0.149	Destabilizing	None	N	0.135	neutral	N	0.377116625	None	None	N
R/L	0.1308	likely_benign	0.139	benign	0.401	Stabilizing	0.072	N	0.315	neutral	None	None	None	None	N
R/M	0.1177	likely_benign	0.1269	benign	0.066	Stabilizing	0.628	D	0.263	neutral	None	None	None	None	N
R/N	0.1745	likely_benign	0.2085	benign	0.236	Stabilizing	0.001	N	0.173	neutral	None	None	None	None	N
R/P	0.4233	ambiguous	0.4335	ambiguous	0.235	Stabilizing	0.356	N	0.293	neutral	None	None	None	None	N
R/Q	0.074	likely_benign	0.0785	benign	0.068	Stabilizing	0.038	N	0.226	neutral	None	None	None	None	N
R/S	0.1429	likely_benign	0.1576	benign	-0.252	Destabilizing	0.012	N	0.291	neutral	N	0.426121293	None	None	N
R/T	0.0773	likely_benign	0.084	benign	-0.038	Destabilizing	0.055	N	0.293	neutral	N	0.444264337	None	None	N
R/V	0.1572	likely_benign	0.1774	benign	0.235	Stabilizing	0.072	N	0.313	neutral	None	None	None	None	N
R/W	0.1289	likely_benign	0.1299	benign	-0.261	Destabilizing	0.864	D	0.202	neutral	None	None	None	None	N
R/Y	0.2101	likely_benign	0.2382	benign	0.129	Stabilizing	0.001	N	0.254	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.