TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27635	83128;83129;83130	chr2:178563229;178563228;178563227	chr2:179427956;179427955;179427954
N2AB	25994	78205;78206;78207	chr2:178563229;178563228;178563227	chr2:179427956;179427955;179427954
N2A	25067	75424;75425;75426	chr2:178563229;178563228;178563227	chr2:179427956;179427955;179427954
N2B	18570	55933;55934;55935	chr2:178563229;178563228;178563227	chr2:179427956;179427955;179427954
Novex-1	18695	56308;56309;56310	chr2:178563229;178563228;178563227	chr2:179427956;179427955;179427954
Novex-2	18762	56509;56510;56511	chr2:178563229;178563228;178563227	chr2:179427956;179427955;179427954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-89
• Domain position: 66
• Structural Position: 96
• Q(SASA): 0.9081
• 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
K/E	None	None	None	N	0.267	0.075	0.19670166235	gnomAD-4.0.0	3.18283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71749E-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
K/A	0.1429	likely_benign	0.14	benign	-0.048	Destabilizing	0.035	N	0.381	neutral	None	None	None	None	N
K/C	0.4596	ambiguous	0.4985	ambiguous	-0.522	Destabilizing	0.935	D	0.459	neutral	None	None	None	None	N
K/D	0.1829	likely_benign	0.1635	benign	-0.182	Destabilizing	0.081	N	0.426	neutral	None	None	None	None	N
K/E	0.1116	likely_benign	0.098	benign	-0.199	Destabilizing	None	N	0.267	neutral	N	0.490158837	None	None	N
K/F	0.6467	likely_pathogenic	0.6593	pathogenic	-0.42	Destabilizing	0.555	D	0.472	neutral	None	None	None	None	N
K/G	0.1383	likely_benign	0.1419	benign	-0.161	Destabilizing	0.081	N	0.419	neutral	None	None	None	None	N
K/H	0.1623	likely_benign	0.1722	benign	-0.255	Destabilizing	0.001	N	0.427	neutral	None	None	None	None	N
K/I	0.3847	ambiguous	0.3601	ambiguous	0.163	Stabilizing	0.555	D	0.487	neutral	None	None	None	None	N
K/L	0.2683	likely_benign	0.2615	benign	0.163	Stabilizing	0.149	N	0.46	neutral	None	None	None	None	N
K/M	0.1929	likely_benign	0.1854	benign	-0.118	Destabilizing	0.78	D	0.439	neutral	N	0.501109288	None	None	N
K/N	0.1316	likely_benign	0.1296	benign	-0.06	Destabilizing	None	N	0.288	neutral	N	0.404846652	None	None	N
K/P	0.4991	ambiguous	0.4541	ambiguous	0.115	Stabilizing	0.555	D	0.457	neutral	None	None	None	None	N
K/Q	0.0892	likely_benign	0.0918	benign	-0.199	Destabilizing	0.004	N	0.315	neutral	N	0.518596232	None	None	N
K/R	0.0821	likely_benign	0.0855	benign	-0.136	Destabilizing	0.062	N	0.397	neutral	N	0.47432538	None	None	N
K/S	0.1482	likely_benign	0.1451	benign	-0.455	Destabilizing	0.002	N	0.291	neutral	None	None	None	None	N
K/T	0.1096	likely_benign	0.1032	benign	-0.356	Destabilizing	0.062	N	0.439	neutral	N	0.470977164	None	None	N
K/V	0.2745	likely_benign	0.2543	benign	0.115	Stabilizing	0.38	N	0.463	neutral	None	None	None	None	N
K/W	0.6555	likely_pathogenic	0.6785	pathogenic	-0.512	Destabilizing	0.935	D	0.537	neutral	None	None	None	None	N
K/Y	0.4296	ambiguous	0.439	ambiguous	-0.158	Destabilizing	0.38	N	0.475	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.