TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7454	22585;22586;22587	chr2:178722427;178722426;178722425	chr2:179587154;179587153;179587152
N2AB	7137	21634;21635;21636	chr2:178722427;178722426;178722425	chr2:179587154;179587153;179587152
N2A	6210	18853;18854;18855	chr2:178722427;178722426;178722425	chr2:179587154;179587153;179587152
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-59
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2709
• 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	rs727504464	-1.295	None	N	0.233	0.155	0.19670166235	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/K	rs727504464	-1.295	None	N	0.233	0.155	0.19670166235	gnomAD-4.0.0	5.47466E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19703E-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
R/A	0.6123	likely_pathogenic	0.6131	pathogenic	-1.271	Destabilizing	0.035	N	0.505	neutral	None	None	None	None	N
R/C	0.2859	likely_benign	0.2392	benign	-1.151	Destabilizing	0.935	D	0.621	neutral	None	None	None	None	N
R/D	0.8994	likely_pathogenic	0.9046	pathogenic	-0.117	Destabilizing	0.149	N	0.593	neutral	None	None	None	None	N
R/E	0.5136	ambiguous	0.5283	ambiguous	0.032	Stabilizing	0.035	N	0.559	neutral	None	None	None	None	N
R/F	0.7321	likely_pathogenic	0.7173	pathogenic	-1.049	Destabilizing	0.791	D	0.619	neutral	None	None	None	None	N
R/G	0.5362	ambiguous	0.5482	ambiguous	-1.596	Destabilizing	0.117	N	0.553	neutral	N	0.49750834	None	None	N
R/H	0.1291	likely_benign	0.1327	benign	-1.851	Destabilizing	0.555	D	0.535	neutral	None	None	None	None	N
R/I	0.4303	ambiguous	0.4087	ambiguous	-0.381	Destabilizing	0.484	N	0.606	neutral	N	0.500355496	None	None	N
R/K	0.0794	likely_benign	0.0836	benign	-1.002	Destabilizing	None	N	0.233	neutral	N	0.37777556	None	None	N
R/L	0.3361	likely_benign	0.3173	benign	-0.381	Destabilizing	0.149	N	0.553	neutral	None	None	None	None	N
R/M	0.3918	ambiguous	0.3856	ambiguous	-0.679	Destabilizing	0.791	D	0.587	neutral	None	None	None	None	N
R/N	0.8017	likely_pathogenic	0.8106	pathogenic	-0.54	Destabilizing	0.149	N	0.553	neutral	None	None	None	None	N
R/P	0.9593	likely_pathogenic	0.9681	pathogenic	-0.659	Destabilizing	0.555	D	0.609	neutral	None	None	None	None	N
R/Q	0.1287	likely_benign	0.1262	benign	-0.686	Destabilizing	0.081	N	0.599	neutral	None	None	None	None	N
R/S	0.6992	likely_pathogenic	0.7067	pathogenic	-1.471	Destabilizing	0.062	N	0.523	neutral	N	0.510079186	None	None	N
R/T	0.5305	ambiguous	0.543	ambiguous	-1.119	Destabilizing	0.117	N	0.532	neutral	N	0.521435492	None	None	N
R/V	0.5353	ambiguous	0.5127	ambiguous	-0.659	Destabilizing	0.38	N	0.601	neutral	None	None	None	None	N
R/W	0.3096	likely_benign	0.2964	benign	-0.614	Destabilizing	0.935	D	0.644	neutral	None	None	None	None	N
R/Y	0.5771	likely_pathogenic	0.5581	ambiguous	-0.368	Destabilizing	0.791	D	0.599	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.