TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6365	19318;19319;19320	chr2:178728945;178728944;178728943	chr2:179593672;179593671;179593670
N2AB	6048	18367;18368;18369	chr2:178728945;178728944;178728943	chr2:179593672;179593671;179593670
N2A	5121	15586;15587;15588	chr2:178728945;178728944;178728943	chr2:179593672;179593671;179593670
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: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-47
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.4391
• 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	rs762632541	-0.232	0.961	N	0.582	0.338	0.359963025489	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
Q/R	rs762632541	-0.232	0.961	N	0.582	0.338	0.359963025489	gnomAD-4.0.0	1.59546E-06	None	None	None	None	N	None	0	0	None	0	2.77979E-05	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	0.4614	ambiguous	0.4764	ambiguous	-0.852	Destabilizing	0.985	D	0.633	neutral	None	None	None	None	N
Q/C	0.7977	likely_pathogenic	0.8023	pathogenic	-0.503	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
Q/D	0.7645	likely_pathogenic	0.8062	pathogenic	-1.64	Destabilizing	0.993	D	0.566	neutral	None	None	None	None	N
Q/E	0.0914	likely_benign	0.0983	benign	-1.457	Destabilizing	0.953	D	0.469	neutral	N	0.491519566	None	None	N
Q/F	0.7311	likely_pathogenic	0.7571	pathogenic	-0.39	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
Q/G	0.6993	likely_pathogenic	0.7276	pathogenic	-1.257	Destabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	N
Q/H	0.3422	ambiguous	0.3849	ambiguous	-1.021	Destabilizing	0.999	D	0.619	neutral	N	0.507510476	None	None	N
Q/I	0.3183	likely_benign	0.325	benign	0.217	Stabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
Q/K	0.1567	likely_benign	0.1663	benign	-0.603	Destabilizing	0.4	N	0.382	neutral	N	0.519762173	None	None	N
Q/L	0.1669	likely_benign	0.1828	benign	0.217	Stabilizing	0.99	D	0.705	prob.neutral	D	0.525864213	None	None	N
Q/M	0.3801	ambiguous	0.4033	ambiguous	0.527	Stabilizing	0.999	D	0.623	neutral	None	None	None	None	N
Q/N	0.6126	likely_pathogenic	0.6529	pathogenic	-1.336	Destabilizing	0.993	D	0.587	neutral	None	None	None	None	N
Q/P	0.9636	likely_pathogenic	0.9766	pathogenic	-0.11	Destabilizing	0.999	D	0.701	prob.neutral	D	0.541743976	None	None	N
Q/R	0.1557	likely_benign	0.1724	benign	-0.595	Destabilizing	0.961	D	0.582	neutral	N	0.500677767	None	None	N
Q/S	0.522	ambiguous	0.5472	ambiguous	-1.466	Destabilizing	0.985	D	0.579	neutral	None	None	None	None	N
Q/T	0.3411	ambiguous	0.3481	ambiguous	-1.095	Destabilizing	0.993	D	0.668	neutral	None	None	None	None	N
Q/V	0.2312	likely_benign	0.242	benign	-0.11	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
Q/W	0.6844	likely_pathogenic	0.711	pathogenic	-0.353	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
Q/Y	0.5672	likely_pathogenic	0.6078	pathogenic	-0.038	Destabilizing	0.999	D	0.716	prob.delet.	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.