TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19101	57526;57527;57528	chr2:178597781;178597780;178597779	chr2:179462508;179462507;179462506
N2AB	17460	52603;52604;52605	chr2:178597781;178597780;178597779	chr2:179462508;179462507;179462506
N2A	16533	49822;49823;49824	chr2:178597781;178597780;178597779	chr2:179462508;179462507;179462506
N2B	10036	30331;30332;30333	chr2:178597781;178597780;178597779	chr2:179462508;179462507;179462506
Novex-1	10161	30706;30707;30708	chr2:178597781;178597780;178597779	chr2:179462508;179462507;179462506
Novex-2	10228	30907;30908;30909	chr2:178597781;178597780;178597779	chr2:179462508;179462507;179462506
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-117
• Domain position: 7
• Structural Position: 11
• Q(SASA): 0.6183
• Predicted PPI site: I

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/G	rs763313986	-0.381	0.959	N	0.447	0.327	0.230578612272	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
R/G	rs763313986	-0.381	0.959	N	0.447	0.327	0.230578612272	gnomAD-4.0.0	1.59258E-06	None	None	None	None	I	None	5.66123E-05	0	None	0	0	None	0	0	0	0	0
R/S	None	None	0.92	N	0.431	0.223	0.250039746154	gnomAD-4.0.0	1.59256E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85992E-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	0.8136	likely_pathogenic	0.8488	pathogenic	-0.322	Destabilizing	0.863	D	0.38	neutral	None	None	None	None	I
R/C	0.4005	ambiguous	0.4954	ambiguous	-0.354	Destabilizing	0.999	D	0.419	neutral	None	None	None	None	I
R/D	0.9228	likely_pathogenic	0.9408	pathogenic	0.032	Stabilizing	0.969	D	0.435	neutral	None	None	None	None	I
R/E	0.7301	likely_pathogenic	0.7859	pathogenic	0.142	Stabilizing	0.863	D	0.351	neutral	None	None	None	None	I
R/F	0.8864	likely_pathogenic	0.9118	pathogenic	-0.259	Destabilizing	0.991	D	0.406	neutral	None	None	None	None	I
R/G	0.5976	likely_pathogenic	0.6666	pathogenic	-0.604	Destabilizing	0.959	D	0.447	neutral	N	0.399237683	None	None	I
R/H	0.1756	likely_benign	0.216	benign	-1.021	Destabilizing	0.1	N	0.266	neutral	None	None	None	None	I
R/I	0.6975	likely_pathogenic	0.7521	pathogenic	0.415	Stabilizing	0.996	D	0.415	neutral	N	0.440604303	None	None	I
R/K	0.1607	likely_benign	0.1701	benign	-0.373	Destabilizing	0.061	N	0.163	neutral	N	0.358025779	None	None	I
R/L	0.6356	likely_pathogenic	0.6952	pathogenic	0.415	Stabilizing	0.969	D	0.446	neutral	None	None	None	None	I
R/M	0.6416	likely_pathogenic	0.7048	pathogenic	-0.042	Destabilizing	0.997	D	0.426	neutral	None	None	None	None	I
R/N	0.8347	likely_pathogenic	0.8595	pathogenic	-0.007	Destabilizing	0.939	D	0.381	neutral	None	None	None	None	I
R/P	0.9751	likely_pathogenic	0.9811	pathogenic	0.192	Stabilizing	0.997	D	0.418	neutral	None	None	None	None	I
R/Q	0.1985	likely_benign	0.2374	benign	-0.107	Destabilizing	0.939	D	0.438	neutral	None	None	None	None	I
R/S	0.816	likely_pathogenic	0.8575	pathogenic	-0.569	Destabilizing	0.92	D	0.431	neutral	N	0.40450743	None	None	I
R/T	0.5798	likely_pathogenic	0.644	pathogenic	-0.288	Destabilizing	0.959	D	0.453	neutral	N	0.389194048	None	None	I
R/V	0.7555	likely_pathogenic	0.7943	pathogenic	0.192	Stabilizing	0.991	D	0.421	neutral	None	None	None	None	I
R/W	0.5122	ambiguous	0.6141	pathogenic	-0.094	Destabilizing	0.999	D	0.473	neutral	None	None	None	None	I
R/Y	0.7455	likely_pathogenic	0.7908	pathogenic	0.249	Stabilizing	0.982	D	0.425	neutral	None	None	None	None	I

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.