TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25598	77017;77018;77019	chr2:178569340;178569339;178569338	chr2:179434067;179434066;179434065
N2AB	23957	72094;72095;72096	chr2:178569340;178569339;178569338	chr2:179434067;179434066;179434065
N2A	23030	69313;69314;69315	chr2:178569340;178569339;178569338	chr2:179434067;179434066;179434065
N2B	16533	49822;49823;49824	chr2:178569340;178569339;178569338	chr2:179434067;179434066;179434065
Novex-1	16658	50197;50198;50199	chr2:178569340;178569339;178569338	chr2:179434067;179434066;179434065
Novex-2	16725	50398;50399;50400	chr2:178569340;178569339;178569338	chr2:179434067;179434066;179434065
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-135
• Domain position: 85
• Structural Position: 177
• Q(SASA): 0.9222
• Predicted PPI site: I

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	rs763761448	-0.001	0.997	D	0.761	0.541	0.856409917051	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	8.91E-06	0
V/I	rs763761448	-0.001	0.997	D	0.761	0.541	0.856409917051	gnomAD-4.0.0	1.59212E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4339E-05	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	0.971	likely_pathogenic	0.974	pathogenic	-1.916	Destabilizing	0.999	D	0.783	deleterious	D	0.636162849	None	None	I
V/C	0.9835	likely_pathogenic	0.9867	pathogenic	-1.697	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
V/D	0.9993	likely_pathogenic	0.9993	pathogenic	-2.579	Highly Destabilizing	1.0	D	0.826	deleterious	D	0.636768262	None	None	I
V/E	0.9978	likely_pathogenic	0.9979	pathogenic	-2.531	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
V/F	0.9802	likely_pathogenic	0.9821	pathogenic	-1.488	Destabilizing	1.0	D	0.865	deleterious	D	0.619911323	None	None	I
V/G	0.9804	likely_pathogenic	0.98	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.792	deleterious	D	0.636768262	None	None	I
V/H	0.9994	likely_pathogenic	0.9994	pathogenic	-1.794	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
V/I	0.1489	likely_benign	0.1671	benign	-1.002	Destabilizing	0.997	D	0.761	deleterious	D	0.5248425329999999	None	None	I
V/K	0.9986	likely_pathogenic	0.9987	pathogenic	-1.641	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
V/L	0.9414	likely_pathogenic	0.9542	pathogenic	-1.002	Destabilizing	0.997	D	0.796	deleterious	D	0.608606694	None	None	I
V/M	0.9496	likely_pathogenic	0.9584	pathogenic	-0.948	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
V/N	0.9951	likely_pathogenic	0.995	pathogenic	-1.667	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
V/P	0.9957	likely_pathogenic	0.9965	pathogenic	-1.276	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
V/Q	0.998	likely_pathogenic	0.9981	pathogenic	-1.827	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/R	0.9973	likely_pathogenic	0.9975	pathogenic	-1.131	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
V/S	0.9866	likely_pathogenic	0.9863	pathogenic	-2.16	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
V/T	0.9671	likely_pathogenic	0.9673	pathogenic	-2.004	Highly Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	I
V/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.758	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
V/Y	0.9981	likely_pathogenic	0.9983	pathogenic	-1.46	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I

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.