TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27982	84169;84170;84171	chr2:178562188;178562187;178562186	chr2:179426915;179426914;179426913
N2AB	26341	79246;79247;79248	chr2:178562188;178562187;178562186	chr2:179426915;179426914;179426913
N2A	25414	76465;76466;76467	chr2:178562188;178562187;178562186	chr2:179426915;179426914;179426913
N2B	18917	56974;56975;56976	chr2:178562188;178562187;178562186	chr2:179426915;179426914;179426913
Novex-1	19042	57349;57350;57351	chr2:178562188;178562187;178562186	chr2:179426915;179426914;179426913
Novex-2	19109	57550;57551;57552	chr2:178562188;178562187;178562186	chr2:179426915;179426914;179426913
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-142
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.2698
• 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
I/T	rs773976497	None	0.722	N	0.753	0.556	0.59698544216	gnomAD-4.0.0	2.73825E-06	None	None	None	None	N	None	0	2.24155E-05	None	0	0	None	0	1.73551E-04	0	0	3.31543E-05

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
I/A	0.6331	likely_pathogenic	0.6469	pathogenic	-2.054	Highly Destabilizing	0.011	N	0.516	neutral	None	None	None	None	N
I/C	0.9204	likely_pathogenic	0.9178	pathogenic	-1.635	Destabilizing	0.989	D	0.745	deleterious	None	None	None	None	N
I/D	0.9919	likely_pathogenic	0.9943	pathogenic	-1.547	Destabilizing	0.961	D	0.857	deleterious	None	None	None	None	N
I/E	0.9773	likely_pathogenic	0.9836	pathogenic	-1.312	Destabilizing	0.923	D	0.841	deleterious	None	None	None	None	N
I/F	0.4101	ambiguous	0.3992	ambiguous	-1.234	Destabilizing	0.901	D	0.711	prob.delet.	N	0.512363693	None	None	N
I/G	0.9543	likely_pathogenic	0.9594	pathogenic	-2.555	Highly Destabilizing	0.858	D	0.823	deleterious	None	None	None	None	N
I/H	0.9805	likely_pathogenic	0.9857	pathogenic	-1.834	Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	N
I/K	0.9592	likely_pathogenic	0.9706	pathogenic	-1.409	Destabilizing	0.923	D	0.843	deleterious	None	None	None	None	N
I/L	0.2065	likely_benign	0.1827	benign	-0.611	Destabilizing	0.19	N	0.51	neutral	N	0.450005725	None	None	N
I/M	0.1699	likely_benign	0.1704	benign	-0.8	Destabilizing	0.901	D	0.671	neutral	N	0.488263677	None	None	N
I/N	0.933	likely_pathogenic	0.9542	pathogenic	-1.778	Destabilizing	0.949	D	0.852	deleterious	D	0.529120223	None	None	N
I/P	0.9816	likely_pathogenic	0.9848	pathogenic	-1.074	Destabilizing	0.961	D	0.857	deleterious	None	None	None	None	N
I/Q	0.9678	likely_pathogenic	0.9747	pathogenic	-1.532	Destabilizing	0.961	D	0.848	deleterious	None	None	None	None	N
I/R	0.9359	likely_pathogenic	0.9542	pathogenic	-1.381	Destabilizing	0.961	D	0.852	deleterious	None	None	None	None	N
I/S	0.8859	likely_pathogenic	0.9105	pathogenic	-2.548	Highly Destabilizing	0.565	D	0.82	deleterious	D	0.529120223	None	None	N
I/T	0.6476	likely_pathogenic	0.6916	pathogenic	-2.141	Highly Destabilizing	0.722	D	0.753	deleterious	N	0.510927063	None	None	N
I/V	0.1002	likely_benign	0.101	benign	-1.074	Destabilizing	0.003	N	0.274	neutral	D	0.524746705	None	None	N
I/W	0.9665	likely_pathogenic	0.9645	pathogenic	-1.37	Destabilizing	0.996	D	0.816	deleterious	None	None	None	None	N
I/Y	0.8894	likely_pathogenic	0.8949	pathogenic	-1.126	Destabilizing	0.961	D	0.754	deleterious	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.