TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19649	59170;59171;59172	chr2:178593263;178593262;178593261	chr2:179457990;179457989;179457988
N2AB	18008	54247;54248;54249	chr2:178593263;178593262;178593261	chr2:179457990;179457989;179457988
N2A	17081	51466;51467;51468	chr2:178593263;178593262;178593261	chr2:179457990;179457989;179457988
N2B	10584	31975;31976;31977	chr2:178593263;178593262;178593261	chr2:179457990;179457989;179457988
Novex-1	10709	32350;32351;32352	chr2:178593263;178593262;178593261	chr2:179457990;179457989;179457988
Novex-2	10776	32551;32552;32553	chr2:178593263;178593262;178593261	chr2:179457990;179457989;179457988
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: Fn3-30
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2069
• 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/H	rs886038922	None	None	D	0.205	0.119	0.124217242631	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/H	rs886038922	None	None	D	0.205	0.119	0.124217242631	gnomAD-4.0.0	4.95879E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.7821E-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	0.1935	likely_benign	0.2166	benign	-0.921	Destabilizing	0.035	N	0.401	neutral	None	None	None	None	N
Q/C	0.5895	likely_pathogenic	0.6188	pathogenic	-0.115	Destabilizing	0.935	D	0.624	neutral	None	None	None	None	N
Q/D	0.3995	ambiguous	0.4545	ambiguous	-0.858	Destabilizing	0.035	N	0.388	neutral	None	None	None	None	N
Q/E	0.0621	likely_benign	0.0663	benign	-0.654	Destabilizing	None	N	0.093	neutral	N	0.350417521	None	None	N
Q/F	0.6745	likely_pathogenic	0.7139	pathogenic	-0.27	Destabilizing	0.38	N	0.611	neutral	None	None	None	None	N
Q/G	0.3531	ambiguous	0.3814	ambiguous	-1.36	Destabilizing	0.149	N	0.502	neutral	None	None	None	None	N
Q/H	0.2379	likely_benign	0.2665	benign	-0.926	Destabilizing	None	N	0.205	neutral	D	0.522713973	None	None	N
Q/I	0.3941	ambiguous	0.3837	ambiguous	0.258	Stabilizing	0.555	D	0.604	neutral	None	None	None	None	N
Q/K	0.1569	likely_benign	0.1498	benign	-0.418	Destabilizing	0.027	N	0.424	neutral	N	0.469090131	None	None	N
Q/L	0.1457	likely_benign	0.15	benign	0.258	Stabilizing	0.117	N	0.519	neutral	N	0.486099811	None	None	N
Q/M	0.3402	ambiguous	0.3447	ambiguous	0.629	Stabilizing	0.791	D	0.487	neutral	None	None	None	None	N
Q/N	0.2696	likely_benign	0.3136	benign	-1.048	Destabilizing	0.081	N	0.401	neutral	None	None	None	None	N
Q/P	0.2218	likely_benign	0.2145	benign	-0.107	Destabilizing	0.211	N	0.524	neutral	N	0.483406223	None	None	N
Q/R	0.1654	likely_benign	0.1585	benign	-0.486	Destabilizing	0.117	N	0.423	neutral	N	0.473535946	None	None	N
Q/S	0.1979	likely_benign	0.2258	benign	-1.322	Destabilizing	0.035	N	0.422	neutral	None	None	None	None	N
Q/T	0.2073	likely_benign	0.2141	benign	-0.914	Destabilizing	0.149	N	0.467	neutral	None	None	None	None	N
Q/V	0.2379	likely_benign	0.2373	benign	-0.107	Destabilizing	0.149	N	0.568	neutral	None	None	None	None	N
Q/W	0.6764	likely_pathogenic	0.66	pathogenic	-0.174	Destabilizing	0.935	D	0.598	neutral	None	None	None	None	N
Q/Y	0.4551	ambiguous	0.5004	ambiguous	0.078	Stabilizing	0.235	N	0.539	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.