TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2635	8128;8129;8130	chr2:178771424;178771423;178771422	chr2:179636151;179636150;179636149
N2AB	2635	8128;8129;8130	chr2:178771424;178771423;178771422	chr2:179636151;179636150;179636149
N2A	2635	8128;8129;8130	chr2:178771424;178771423;178771422	chr2:179636151;179636150;179636149
N2B	2589	7990;7991;7992	chr2:178771424;178771423;178771422	chr2:179636151;179636150;179636149
Novex-1	2589	7990;7991;7992	chr2:178771424;178771423;178771422	chr2:179636151;179636150;179636149
Novex-2	2589	7990;7991;7992	chr2:178771424;178771423;178771422	chr2:179636151;179636150;179636149
Novex-3	2635	8128;8129;8130	chr2:178771424;178771423;178771422	chr2:179636151;179636150;179636149

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-16
• Domain position: 15
• Structural Position: 25
• Q(SASA): 0.3501
• 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/R	rs773524537	0.254	0.997	N	0.458	0.381	0.0806252709748	gnomAD-4.0.0	1.59093E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85749E-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	0.5131	ambiguous	0.4827	ambiguous	-0.33	Destabilizing	0.997	D	0.437	neutral	None	None	None	None	N
Q/C	0.9297	likely_pathogenic	0.9218	pathogenic	0.221	Stabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
Q/D	0.5878	likely_pathogenic	0.5796	pathogenic	-0.154	Destabilizing	0.997	D	0.462	neutral	None	None	None	None	N
Q/E	0.0913	likely_benign	0.0916	benign	-0.171	Destabilizing	0.992	D	0.371	neutral	N	0.343407113	None	None	N
Q/F	0.9521	likely_pathogenic	0.9443	pathogenic	-0.463	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
Q/G	0.5215	ambiguous	0.4814	ambiguous	-0.548	Destabilizing	0.997	D	0.535	neutral	None	None	None	None	N
Q/H	0.6776	likely_pathogenic	0.6528	pathogenic	-0.531	Destabilizing	0.999	D	0.574	neutral	N	0.341796872	None	None	N
Q/I	0.8503	likely_pathogenic	0.8263	pathogenic	0.166	Stabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
Q/K	0.2718	likely_benign	0.2245	benign	0.036	Stabilizing	0.997	D	0.423	neutral	N	0.321977543	None	None	N
Q/L	0.4302	ambiguous	0.3898	ambiguous	0.166	Stabilizing	0.997	D	0.535	neutral	N	0.39757878	None	None	N
Q/M	0.6192	likely_pathogenic	0.6032	pathogenic	0.595	Stabilizing	0.999	D	0.573	neutral	None	None	None	None	N
Q/N	0.6327	likely_pathogenic	0.6263	pathogenic	-0.324	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
Q/P	0.9351	likely_pathogenic	0.9081	pathogenic	0.03	Stabilizing	0.999	D	0.631	neutral	N	0.454777463	None	None	N
Q/R	0.3234	likely_benign	0.2635	benign	0.189	Stabilizing	0.997	D	0.458	neutral	N	0.321289573	None	None	N
Q/S	0.5355	ambiguous	0.5151	ambiguous	-0.34	Destabilizing	0.997	D	0.422	neutral	None	None	None	None	N
Q/T	0.5528	ambiguous	0.5155	ambiguous	-0.194	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
Q/V	0.6807	likely_pathogenic	0.6427	pathogenic	0.03	Stabilizing	0.999	D	0.589	neutral	None	None	None	None	N
Q/W	0.9387	likely_pathogenic	0.9178	pathogenic	-0.39	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
Q/Y	0.8945	likely_pathogenic	0.8792	pathogenic	-0.147	Destabilizing	0.999	D	0.624	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.