TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14999	45220;45221;45222	chr2:178621927;178621926;178621925	chr2:179486654;179486653;179486652
N2AB	13358	40297;40298;40299	chr2:178621927;178621926;178621925	chr2:179486654;179486653;179486652
N2A	12431	37516;37517;37518	chr2:178621927;178621926;178621925	chr2:179486654;179486653;179486652
N2B	5934	18025;18026;18027	chr2:178621927;178621926;178621925	chr2:179486654;179486653;179486652
Novex-1	6059	18400;18401;18402	chr2:178621927;178621926;178621925	chr2:179486654;179486653;179486652
Novex-2	6126	18601;18602;18603	chr2:178621927;178621926;178621925	chr2:179486654;179486653;179486652
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-101
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.2085
• 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
V/I	rs1382155901	-0.494	0.37	N	0.235	0.108	0.516770950016	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
V/I	rs1382155901	-0.494	0.37	N	0.235	0.108	0.516770950016	gnomAD-4.0.0	3.19049E-06	None	None	None	None	N	None	0	4.59031E-05	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
V/A	0.5157	ambiguous	0.5454	ambiguous	-2.204	Highly Destabilizing	0.978	D	0.445	neutral	D	0.575633039	None	None	N
V/C	0.8988	likely_pathogenic	0.9076	pathogenic	-1.749	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
V/D	0.8391	likely_pathogenic	0.8428	pathogenic	-2.833	Highly Destabilizing	0.999	D	0.798	deleterious	D	0.577890796	None	None	N
V/E	0.6173	likely_pathogenic	0.6319	pathogenic	-2.693	Highly Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
V/F	0.3893	ambiguous	0.3714	ambiguous	-1.382	Destabilizing	0.997	D	0.773	deleterious	N	0.502895438	None	None	N
V/G	0.6375	likely_pathogenic	0.6618	pathogenic	-2.665	Highly Destabilizing	0.999	D	0.778	deleterious	D	0.659513718	None	None	N
V/H	0.8057	likely_pathogenic	0.8261	pathogenic	-2.313	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/I	0.0954	likely_benign	0.0953	benign	-0.946	Destabilizing	0.37	N	0.235	neutral	N	0.441035801	None	None	N
V/K	0.6769	likely_pathogenic	0.7007	pathogenic	-1.976	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
V/L	0.299	likely_benign	0.3078	benign	-0.946	Destabilizing	0.9	D	0.381	neutral	N	0.510168819	None	None	N
V/M	0.3057	likely_benign	0.3074	benign	-0.894	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
V/N	0.6579	likely_pathogenic	0.7031	pathogenic	-2.103	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
V/P	0.99	likely_pathogenic	0.9882	pathogenic	-1.337	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
V/Q	0.6012	likely_pathogenic	0.6303	pathogenic	-2.082	Highly Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
V/R	0.6144	likely_pathogenic	0.6305	pathogenic	-1.578	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/S	0.5762	likely_pathogenic	0.6282	pathogenic	-2.663	Highly Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	N
V/T	0.4602	ambiguous	0.4916	ambiguous	-2.405	Highly Destabilizing	0.992	D	0.535	neutral	None	None	None	None	N
V/W	0.9418	likely_pathogenic	0.9415	pathogenic	-1.842	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
V/Y	0.7596	likely_pathogenic	0.769	pathogenic	-1.542	Destabilizing	0.999	D	0.779	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.