TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7466	22621;22622;22623	chr2:178722391;178722390;178722389	chr2:179587118;179587117;179587116
N2AB	7149	21670;21671;21672	chr2:178722391;178722390;178722389	chr2:179587118;179587117;179587116
N2A	6222	18889;18890;18891	chr2:178722391;178722390;178722389	chr2:179587118;179587117;179587116
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-59
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.5225
• 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
Q/H	rs1378606339	None	0.01	N	0.19	0.184	0.263612267334	gnomAD-4.0.0	1.59206E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4332E-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
Q/A	0.4041	ambiguous	0.4346	ambiguous	-0.669	Destabilizing	0.482	N	0.259	neutral	None	None	None	None	I
Q/C	0.7845	likely_pathogenic	0.8165	pathogenic	-0.315	Destabilizing	0.985	D	0.432	neutral	None	None	None	None	I
Q/D	0.5928	likely_pathogenic	0.6431	pathogenic	-1.468	Destabilizing	0.561	D	0.211	neutral	None	None	None	None	I
Q/E	0.1021	likely_benign	0.1121	benign	-1.324	Destabilizing	0.572	D	0.243	neutral	N	0.497117387	None	None	I
Q/F	0.7658	likely_pathogenic	0.8093	pathogenic	-0.436	Destabilizing	0.852	D	0.528	neutral	None	None	None	None	I
Q/G	0.4997	ambiguous	0.5342	ambiguous	-1.05	Destabilizing	0.81	D	0.361	neutral	None	None	None	None	I
Q/H	0.2446	likely_benign	0.3049	benign	-1.034	Destabilizing	0.01	N	0.19	neutral	N	0.499485688	None	None	I
Q/I	0.4703	ambiguous	0.5254	ambiguous	0.32	Stabilizing	0.459	N	0.44	neutral	None	None	None	None	I
Q/K	0.1176	likely_benign	0.1444	benign	-0.46	Destabilizing	0.561	D	0.269	neutral	N	0.450382232	None	None	I
Q/L	0.1984	likely_benign	0.2318	benign	0.32	Stabilizing	0.219	N	0.319	neutral	N	0.512164197	None	None	I
Q/M	0.4948	ambiguous	0.5253	ambiguous	0.747	Stabilizing	0.138	N	0.188	neutral	None	None	None	None	I
Q/N	0.484	ambiguous	0.531	ambiguous	-1.199	Destabilizing	0.756	D	0.211	neutral	None	None	None	None	I
Q/P	0.6795	likely_pathogenic	0.6949	pathogenic	0.021	Stabilizing	0.935	D	0.437	neutral	N	0.508800695	None	None	I
Q/R	0.1204	likely_benign	0.1411	benign	-0.471	Destabilizing	0.67	D	0.237	neutral	N	0.481321215	None	None	I
Q/S	0.438	ambiguous	0.4728	ambiguous	-1.253	Destabilizing	0.145	N	0.107	neutral	None	None	None	None	I
Q/T	0.3325	likely_benign	0.37	ambiguous	-0.918	Destabilizing	0.002	N	0.188	neutral	None	None	None	None	I
Q/V	0.3347	likely_benign	0.3766	ambiguous	0.021	Stabilizing	0.007	N	0.263	neutral	None	None	None	None	I
Q/W	0.6166	likely_pathogenic	0.6667	pathogenic	-0.411	Destabilizing	0.046	N	0.319	neutral	None	None	None	None	I
Q/Y	0.5459	ambiguous	0.6104	pathogenic	-0.08	Destabilizing	0.852	D	0.421	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.