TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16190	48793;48794;48795	chr2:178615377;178615376;178615375	chr2:179480104;179480103;179480102
N2AB	14549	43870;43871;43872	chr2:178615377;178615376;178615375	chr2:179480104;179480103;179480102
N2A	13622	41089;41090;41091	chr2:178615377;178615376;178615375	chr2:179480104;179480103;179480102
N2B	7125	21598;21599;21600	chr2:178615377;178615376;178615375	chr2:179480104;179480103;179480102
Novex-1	7250	21973;21974;21975	chr2:178615377;178615376;178615375	chr2:179480104;179480103;179480102
Novex-2	7317	22174;22175;22176	chr2:178615377;178615376;178615375	chr2:179480104;179480103;179480102
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-5
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1222
• 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
Y/H	rs1294316721	-2.711	1.0	D	0.818	0.814	0.822129434029	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Y/H	rs1294316721	-2.711	1.0	D	0.818	0.814	0.822129434029	gnomAD-4.0.0	1.59374E-06	None	None	None	None	N	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
Y/A	0.9986	likely_pathogenic	0.9978	pathogenic	-3.555	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
Y/C	0.9637	likely_pathogenic	0.9462	pathogenic	-1.981	Destabilizing	1.0	D	0.877	deleterious	D	0.853322918	None	None	N
Y/D	0.998	likely_pathogenic	0.9969	pathogenic	-3.857	Highly Destabilizing	1.0	D	0.917	deleterious	D	0.852940017	None	None	N
Y/E	0.9995	likely_pathogenic	0.9992	pathogenic	-3.646	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/F	0.2865	likely_benign	0.2744	benign	-1.384	Destabilizing	0.999	D	0.63	neutral	D	0.65567746	None	None	N
Y/G	0.9942	likely_pathogenic	0.9912	pathogenic	-3.959	Highly Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
Y/H	0.9883	likely_pathogenic	0.9846	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.818	deleterious	D	0.853488097	None	None	N
Y/I	0.9886	likely_pathogenic	0.9852	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/K	0.9993	likely_pathogenic	0.9989	pathogenic	-2.481	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/L	0.9728	likely_pathogenic	0.9661	pathogenic	-2.186	Highly Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
Y/M	0.9912	likely_pathogenic	0.9882	pathogenic	-1.873	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/N	0.9846	likely_pathogenic	0.9795	pathogenic	-3.262	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.853322918	None	None	N
Y/P	0.9996	likely_pathogenic	0.9995	pathogenic	-2.662	Highly Destabilizing	1.0	D	0.943	deleterious	None	None	None	None	N
Y/Q	0.9992	likely_pathogenic	0.9987	pathogenic	-3.02	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/R	0.9967	likely_pathogenic	0.9956	pathogenic	-2.196	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
Y/S	0.994	likely_pathogenic	0.9916	pathogenic	-3.588	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.853322918	None	None	N
Y/T	0.9981	likely_pathogenic	0.9974	pathogenic	-3.263	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
Y/V	0.9798	likely_pathogenic	0.9742	pathogenic	-2.662	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
Y/W	0.8703	likely_pathogenic	0.8359	pathogenic	-0.608	Destabilizing	1.0	D	0.801	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.