TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6913	20962;20963;20964	chr2:178725467;178725466;178725465	chr2:179590194;179590193;179590192
N2AB	6596	20011;20012;20013	chr2:178725467;178725466;178725465	chr2:179590194;179590193;179590192
N2A	5669	17230;17231;17232	chr2:178725467;178725466;178725465	chr2:179590194;179590193;179590192
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-53
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.3802
• 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	None	None	0.991	N	0.455	0.311	0.269111216191	gnomAD-4.0.0	1.59294E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86066E-06	0	0
Q/R	rs1352796608	None	0.719	N	0.389	0.13	0.218112801441	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/R	rs1352796608	None	0.719	N	0.389	0.13	0.218112801441	gnomAD-4.0.0	2.56397E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78927E-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	0.2985	likely_benign	0.271	benign	-0.834	Destabilizing	0.037	N	0.297	neutral	None	None	None	None	N
Q/C	0.5583	ambiguous	0.4845	ambiguous	-0.342	Destabilizing	0.993	D	0.457	neutral	None	None	None	None	N
Q/D	0.547	ambiguous	0.5304	ambiguous	-1.195	Destabilizing	0.932	D	0.377	neutral	None	None	None	None	N
Q/E	0.1057	likely_benign	0.1038	benign	-1.015	Destabilizing	0.679	D	0.361	neutral	N	0.499309543	None	None	N
Q/F	0.5614	ambiguous	0.5149	ambiguous	-0.366	Destabilizing	0.96	D	0.541	neutral	None	None	None	None	N
Q/G	0.4115	ambiguous	0.3787	ambiguous	-1.253	Destabilizing	0.737	D	0.421	neutral	None	None	None	None	N
Q/H	0.1744	likely_benign	0.1456	benign	-1.019	Destabilizing	0.991	D	0.455	neutral	N	0.506083587	None	None	N
Q/I	0.3289	likely_benign	0.3029	benign	0.271	Stabilizing	0.037	N	0.447	neutral	None	None	None	None	N
Q/K	0.1194	likely_benign	0.1121	benign	-0.417	Destabilizing	0.028	N	0.226	neutral	N	0.451345025	None	None	N
Q/L	0.1468	likely_benign	0.1378	benign	0.271	Stabilizing	0.007	N	0.388	neutral	N	0.511508049	None	None	N
Q/M	0.3952	ambiguous	0.3689	ambiguous	0.598	Stabilizing	0.96	D	0.446	neutral	None	None	None	None	N
Q/N	0.3777	ambiguous	0.3443	ambiguous	-1.128	Destabilizing	0.932	D	0.412	neutral	None	None	None	None	N
Q/P	0.8017	likely_pathogenic	0.8155	pathogenic	-0.067	Destabilizing	0.912	D	0.482	neutral	N	0.507431116	None	None	N
Q/R	0.1043	likely_benign	0.094	benign	-0.462	Destabilizing	0.719	D	0.389	neutral	N	0.512372054	None	None	N
Q/S	0.3038	likely_benign	0.2744	benign	-1.293	Destabilizing	0.584	D	0.365	neutral	None	None	None	None	N
Q/T	0.2328	likely_benign	0.2043	benign	-0.909	Destabilizing	0.737	D	0.425	neutral	None	None	None	None	N
Q/V	0.2463	likely_benign	0.2226	benign	-0.067	Destabilizing	0.037	N	0.369	neutral	None	None	None	None	N
Q/W	0.4489	ambiguous	0.3918	ambiguous	-0.269	Destabilizing	0.998	D	0.487	neutral	None	None	None	None	N
Q/Y	0.3521	ambiguous	0.3049	benign	0.018	Stabilizing	0.993	D	0.551	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.