TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18343	55252;55253;55254	chr2:178602375;178602374;178602373	chr2:179467102;179467101;179467100
N2AB	16702	50329;50330;50331	chr2:178602375;178602374;178602373	chr2:179467102;179467101;179467100
N2A	15775	47548;47549;47550	chr2:178602375;178602374;178602373	chr2:179467102;179467101;179467100
N2B	9278	28057;28058;28059	chr2:178602375;178602374;178602373	chr2:179467102;179467101;179467100
Novex-1	9403	28432;28433;28434	chr2:178602375;178602374;178602373	chr2:179467102;179467101;179467100
Novex-2	9470	28633;28634;28635	chr2:178602375;178602374;178602373	chr2:179467102;179467101;179467100
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-21
• Domain position: 72
• Structural Position: 102
• Q(SASA): 0.4623
• 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	rs775796823	-0.496	None	N	0.089	0.105	0.162503812791	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/K	rs775796823	-0.496	None	N	0.089	0.105	0.162503812791	gnomAD-4.0.0	6.37296E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72334E-06	2.86681E-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	0.3895	ambiguous	0.4498	ambiguous	-0.604	Destabilizing	0.035	N	0.315	neutral	None	None	None	None	N
R/C	0.1845	likely_benign	0.2044	benign	-0.531	Destabilizing	0.935	D	0.419	neutral	None	None	None	None	N
R/D	0.7255	likely_pathogenic	0.7669	pathogenic	-0.109	Destabilizing	0.149	N	0.421	neutral	None	None	None	None	N
R/E	0.3617	ambiguous	0.4091	ambiguous	0.064	Stabilizing	0.035	N	0.323	neutral	None	None	None	None	N
R/F	0.6105	likely_pathogenic	0.6538	pathogenic	-0.134	Destabilizing	0.791	D	0.421	neutral	None	None	None	None	N
R/G	0.2374	likely_benign	0.2986	benign	-0.962	Destabilizing	0.117	N	0.373	neutral	N	0.440252879	None	None	N
R/H	0.134	likely_benign	0.1413	benign	-1.358	Destabilizing	0.38	N	0.31	neutral	None	None	None	None	N
R/I	0.3049	likely_benign	0.3286	benign	0.376	Stabilizing	0.555	D	0.443	neutral	None	None	None	None	N
R/K	0.0889	likely_benign	0.1	benign	-0.55	Destabilizing	None	N	0.089	neutral	N	0.401963849	None	None	N
R/L	0.266	likely_benign	0.2961	benign	0.376	Stabilizing	0.149	N	0.373	neutral	None	None	None	None	N
R/M	0.2723	likely_benign	0.3165	benign	-0.189	Destabilizing	0.484	N	0.365	neutral	N	0.426091503	None	None	N
R/N	0.5664	likely_pathogenic	0.6199	pathogenic	-0.292	Destabilizing	0.149	N	0.293	neutral	None	None	None	None	N
R/P	0.8535	likely_pathogenic	0.8861	pathogenic	0.07	Stabilizing	0.555	D	0.416	neutral	None	None	None	None	N
R/Q	0.1021	likely_benign	0.1112	benign	-0.255	Destabilizing	0.002	N	0.253	neutral	None	None	None	None	N
R/S	0.4773	ambiguous	0.5502	ambiguous	-0.901	Destabilizing	0.062	N	0.317	neutral	N	0.403059927	None	None	N
R/T	0.2424	likely_benign	0.2822	benign	-0.524	Destabilizing	0.117	N	0.335	neutral	N	0.391778567	None	None	N
R/V	0.3603	ambiguous	0.3839	ambiguous	0.07	Stabilizing	0.149	N	0.449	neutral	None	None	None	None	N
R/W	0.2443	likely_benign	0.2859	benign	0.151	Stabilizing	0.915	D	0.471	neutral	N	0.483158294	None	None	N
R/Y	0.4882	ambiguous	0.5248	ambiguous	0.408	Stabilizing	0.555	D	0.401	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.