TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5317	16174;16175;16176	chr2:178733344;178733343;178733342	chr2:179598071;179598070;179598069
N2AB	5000	15223;15224;15225	chr2:178733344;178733343;178733342	chr2:179598071;179598070;179598069
N2A	4073	12442;12443;12444	chr2:178733344;178733343;178733342	chr2:179598071;179598070;179598069
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-36
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.3573
• 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
Q/E	rs1210762968	-1.363	0.425	N	0.359	0.135	0.281381271821	gnomAD-4.0.0	4.10532E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39678E-06	0	0
Q/P	rs1230882379	None	0.784	D	0.535	0.404	0.362960570912	gnomAD-4.0.0	3.18257E-06	None	None	None	None	N	None	1.13084E-04	0	None	0	0	None	0	0	0	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
Q/A	0.2857	likely_benign	0.2773	benign	-0.672	Destabilizing	0.176	N	0.321	neutral	None	None	None	None	N
Q/C	0.6455	likely_pathogenic	0.5984	pathogenic	-0.461	Destabilizing	0.981	D	0.559	neutral	None	None	None	None	N
Q/D	0.65	likely_pathogenic	0.647	pathogenic	-1.884	Destabilizing	0.495	N	0.343	neutral	None	None	None	None	N
Q/E	0.1118	likely_benign	0.1184	benign	-1.689	Destabilizing	0.425	N	0.359	neutral	N	0.468534326	None	None	N
Q/F	0.6479	likely_pathogenic	0.6295	pathogenic	-0.262	Destabilizing	0.944	D	0.59	neutral	None	None	None	None	N
Q/G	0.4385	ambiguous	0.4308	ambiguous	-1.082	Destabilizing	0.329	N	0.475	neutral	None	None	None	None	N
Q/H	0.2329	likely_benign	0.2198	benign	-1.009	Destabilizing	0.975	D	0.489	neutral	N	0.495744649	None	None	N
Q/I	0.3339	likely_benign	0.3277	benign	0.409	Stabilizing	0.543	D	0.529	neutral	None	None	None	None	N
Q/K	0.1612	likely_benign	0.1578	benign	-0.599	Destabilizing	0.425	N	0.366	neutral	N	0.458389956	None	None	N
Q/L	0.1511	likely_benign	0.1477	benign	0.409	Stabilizing	0.27	N	0.467	neutral	N	0.468678129	None	None	N
Q/M	0.3405	ambiguous	0.3318	benign	0.662	Stabilizing	0.944	D	0.471	neutral	None	None	None	None	N
Q/N	0.3882	ambiguous	0.3663	ambiguous	-1.38	Destabilizing	0.704	D	0.344	neutral	None	None	None	None	N
Q/P	0.9032	likely_pathogenic	0.8978	pathogenic	0.079	Stabilizing	0.784	D	0.535	neutral	D	0.531368121	None	None	N
Q/R	0.1547	likely_benign	0.1575	benign	-0.682	Destabilizing	0.642	D	0.343	neutral	N	0.431352856	None	None	N
Q/S	0.2817	likely_benign	0.269	benign	-1.442	Destabilizing	0.013	N	0.136	neutral	None	None	None	None	N
Q/T	0.2076	likely_benign	0.202	benign	-1.066	Destabilizing	0.004	N	0.228	neutral	None	None	None	None	N
Q/V	0.2319	likely_benign	0.2343	benign	0.079	Stabilizing	0.013	N	0.341	neutral	None	None	None	None	N
Q/W	0.5921	likely_pathogenic	0.5817	pathogenic	-0.35	Destabilizing	0.995	D	0.567	neutral	None	None	None	None	N
Q/Y	0.4281	ambiguous	0.4045	ambiguous	0.029	Stabilizing	0.981	D	0.581	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.