TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35717	107374;107375;107376	chr2:178528602;178528601;178528600	chr2:179393329;179393328;179393327
N2AB	34076	102451;102452;102453	chr2:178528602;178528601;178528600	chr2:179393329;179393328;179393327
N2A	33149	99670;99671;99672	chr2:178528602;178528601;178528600	chr2:179393329;179393328;179393327
N2B	26652	80179;80180;80181	chr2:178528602;178528601;178528600	chr2:179393329;179393328;179393327
Novex-1	26777	80554;80555;80556	chr2:178528602;178528601;178528600	chr2:179393329;179393328;179393327
Novex-2	26844	80755;80756;80757	chr2:178528602;178528601;178528600	chr2:179393329;179393328;179393327
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-168
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.7404
• 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/L	None	None	0.997	N	0.509	0.509	0.433823933641	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
Q/A	0.546	ambiguous	0.5351	ambiguous	-0.445	Destabilizing	0.997	D	0.468	neutral	None	None	None	None	N
Q/C	0.9103	likely_pathogenic	0.9158	pathogenic	0.238	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
Q/D	0.6153	likely_pathogenic	0.5911	pathogenic	-0.267	Destabilizing	0.997	D	0.517	neutral	None	None	None	None	N
Q/E	0.1107	likely_benign	0.1075	benign	-0.245	Destabilizing	0.992	D	0.387	neutral	N	0.403621996	None	None	N
Q/F	0.9398	likely_pathogenic	0.9387	pathogenic	-0.427	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
Q/G	0.5139	ambiguous	0.4963	ambiguous	-0.723	Destabilizing	0.997	D	0.509	neutral	None	None	None	None	N
Q/H	0.55	ambiguous	0.5471	ambiguous	-0.706	Destabilizing	0.999	D	0.588	neutral	N	0.435603915	None	None	N
Q/I	0.8078	likely_pathogenic	0.7984	pathogenic	0.226	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
Q/K	0.1615	likely_benign	0.1541	benign	-0.118	Destabilizing	0.997	D	0.471	neutral	N	0.409974752	None	None	N
Q/L	0.4106	ambiguous	0.4101	ambiguous	0.226	Stabilizing	0.997	D	0.509	neutral	N	0.458035972	None	None	N
Q/M	0.6244	likely_pathogenic	0.6237	pathogenic	0.72	Stabilizing	0.999	D	0.587	neutral	None	None	None	None	N
Q/N	0.5021	ambiguous	0.4823	ambiguous	-0.502	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
Q/P	0.8726	likely_pathogenic	0.8647	pathogenic	0.033	Stabilizing	0.999	D	0.605	neutral	N	0.457782482	None	None	N
Q/R	0.231	likely_benign	0.2225	benign	-0.005	Destabilizing	0.997	D	0.505	neutral	N	0.458152701	None	None	N
Q/S	0.5557	ambiguous	0.5444	ambiguous	-0.539	Destabilizing	0.997	D	0.479	neutral	None	None	None	None	N
Q/T	0.551	ambiguous	0.5369	ambiguous	-0.339	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
Q/V	0.6536	likely_pathogenic	0.646	pathogenic	0.033	Stabilizing	0.999	D	0.549	neutral	None	None	None	None	N
Q/W	0.8843	likely_pathogenic	0.8769	pathogenic	-0.339	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
Q/Y	0.8303	likely_pathogenic	0.8234	pathogenic	-0.111	Destabilizing	0.999	D	0.6	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.