TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6726	20401;20402;20403	chr2:178727189;178727188;178727187	chr2:179591916;179591915;179591914
N2AB	6409	19450;19451;19452	chr2:178727189;178727188;178727187	chr2:179591916;179591915;179591914
N2A	5482	16669;16670;16671	chr2:178727189;178727188;178727187	chr2:179591916;179591915;179591914
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-51
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.4049
• 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	rs1159916010	None	0.669	N	0.527	0.324	0.257292322809	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/R	rs1159916010	None	0.669	N	0.527	0.324	0.257292322809	gnomAD-4.0.0	6.5735E-06	None	None	None	None	N	None	2.41243E-05	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	0.2839	likely_benign	0.2898	benign	-0.324	Destabilizing	0.688	D	0.507	neutral	None	None	None	None	N
Q/C	0.7404	likely_pathogenic	0.742	pathogenic	-0.145	Destabilizing	0.998	D	0.589	neutral	None	None	None	None	N
Q/D	0.3561	ambiguous	0.397	ambiguous	-1.482	Destabilizing	0.525	D	0.5	neutral	None	None	None	None	N
Q/E	0.0599	likely_benign	0.0685	benign	-1.387	Destabilizing	0.002	N	0.223	neutral	N	0.377559342	None	None	N
Q/F	0.6588	likely_pathogenic	0.686	pathogenic	-0.322	Destabilizing	0.991	D	0.594	neutral	None	None	None	None	N
Q/G	0.4014	ambiguous	0.4196	ambiguous	-0.646	Destabilizing	0.842	D	0.562	neutral	None	None	None	None	N
Q/H	0.1833	likely_benign	0.182	benign	-0.766	Destabilizing	0.966	D	0.541	neutral	N	0.48884462	None	None	N
Q/I	0.3689	ambiguous	0.381	ambiguous	0.483	Stabilizing	0.974	D	0.601	neutral	None	None	None	None	N
Q/K	0.1242	likely_benign	0.1361	benign	-0.185	Destabilizing	0.022	N	0.206	neutral	N	0.453499895	None	None	N
Q/L	0.1642	likely_benign	0.1684	benign	0.483	Stabilizing	0.801	D	0.562	neutral	N	0.451979743	None	None	N
Q/M	0.3743	ambiguous	0.3785	ambiguous	0.912	Stabilizing	0.991	D	0.537	neutral	None	None	None	None	N
Q/N	0.3136	likely_benign	0.3437	ambiguous	-0.845	Destabilizing	0.842	D	0.481	neutral	None	None	None	None	N
Q/P	0.7646	likely_pathogenic	0.7972	pathogenic	0.245	Stabilizing	0.891	D	0.551	neutral	D	0.532384754	None	None	N
Q/R	0.1241	likely_benign	0.1326	benign	-0.121	Destabilizing	0.669	D	0.527	neutral	N	0.411901202	None	None	N
Q/S	0.2658	likely_benign	0.2779	benign	-0.838	Destabilizing	0.688	D	0.531	neutral	None	None	None	None	N
Q/T	0.1801	likely_benign	0.1859	benign	-0.571	Destabilizing	0.842	D	0.537	neutral	None	None	None	None	N
Q/V	0.2408	likely_benign	0.2499	benign	0.245	Stabilizing	0.915	D	0.541	neutral	None	None	None	None	N
Q/W	0.5153	ambiguous	0.5462	ambiguous	-0.335	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	N
Q/Y	0.424	ambiguous	0.4593	ambiguous	0.045	Stabilizing	0.991	D	0.598	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.