TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5122	15589;15590;15591	chr2:178734460;178734459;178734458	chr2:179599187;179599186;179599185
N2AB	4805	14638;14639;14640	chr2:178734460;178734459;178734458	chr2:179599187;179599186;179599185
N2A	3878	11857;11858;11859	chr2:178734460;178734459;178734458	chr2:179599187;179599186;179599185
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-34
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.542
• 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	rs754945452	-0.521	0.061	N	0.147	0.135	0.204665344411	gnomAD-4.0.0	3.18317E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86623E-05	0
R/S	rs1275710464	None	0.826	N	0.301	0.311	0.267299060538	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/S	rs1275710464	None	0.826	N	0.301	0.311	0.267299060538	gnomAD-4.0.0	6.57056E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46972E-05	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
R/A	0.6227	likely_pathogenic	0.7398	pathogenic	-0.933	Destabilizing	0.863	D	0.303	neutral	None	None	None	None	N
R/C	0.2436	likely_benign	0.3228	benign	-1.035	Destabilizing	0.999	D	0.337	neutral	None	None	None	None	N
R/D	0.8347	likely_pathogenic	0.9011	pathogenic	0.063	Stabilizing	0.884	D	0.32	neutral	None	None	None	None	N
R/E	0.5864	likely_pathogenic	0.6723	pathogenic	0.213	Stabilizing	0.863	D	0.283	neutral	None	None	None	None	N
R/F	0.7132	likely_pathogenic	0.8214	pathogenic	-0.744	Destabilizing	0.997	D	0.33	neutral	None	None	None	None	N
R/G	0.4979	ambiguous	0.6298	pathogenic	-1.223	Destabilizing	0.826	D	0.334	neutral	N	0.509599753	None	None	N
R/H	0.111	likely_benign	0.1337	benign	-1.351	Destabilizing	0.991	D	0.343	neutral	None	None	None	None	N
R/I	0.431	ambiguous	0.5257	ambiguous	-0.15	Destabilizing	0.996	D	0.337	neutral	N	0.51361182	None	None	N
R/K	0.1181	likely_benign	0.1449	benign	-0.575	Destabilizing	0.061	N	0.147	neutral	N	0.416768547	None	None	N
R/L	0.35	ambiguous	0.4352	ambiguous	-0.15	Destabilizing	0.969	D	0.309	neutral	None	None	None	None	N
R/M	0.4891	ambiguous	0.5889	pathogenic	-0.66	Destabilizing	0.997	D	0.321	neutral	None	None	None	None	N
R/N	0.6796	likely_pathogenic	0.7879	pathogenic	-0.429	Destabilizing	0.079	N	0.149	neutral	None	None	None	None	N
R/P	0.9559	likely_pathogenic	0.9747	pathogenic	-0.393	Destabilizing	0.997	D	0.305	neutral	None	None	None	None	N
R/Q	0.1221	likely_benign	0.1417	benign	-0.487	Destabilizing	0.939	D	0.322	neutral	None	None	None	None	N
R/S	0.6137	likely_pathogenic	0.7342	pathogenic	-1.242	Destabilizing	0.826	D	0.301	neutral	N	0.490592508	None	None	N
R/T	0.424	ambiguous	0.5331	ambiguous	-0.897	Destabilizing	0.92	D	0.306	neutral	N	0.465772928	None	None	N
R/V	0.4838	ambiguous	0.5874	pathogenic	-0.393	Destabilizing	0.991	D	0.324	neutral	None	None	None	None	N
R/W	0.338	likely_benign	0.4222	ambiguous	-0.442	Destabilizing	0.999	D	0.449	neutral	None	None	None	None	N
R/Y	0.5328	ambiguous	0.6565	pathogenic	-0.173	Destabilizing	0.997	D	0.325	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.