TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22082	66469;66470;66471	chr2:178582125;178582124;178582123	chr2:179446852;179446851;179446850
N2AB	20441	61546;61547;61548	chr2:178582125;178582124;178582123	chr2:179446852;179446851;179446850
N2A	19514	58765;58766;58767	chr2:178582125;178582124;178582123	chr2:179446852;179446851;179446850
N2B	13017	39274;39275;39276	chr2:178582125;178582124;178582123	chr2:179446852;179446851;179446850
Novex-1	13142	39649;39650;39651	chr2:178582125;178582124;178582123	chr2:179446852;179446851;179446850
Novex-2	13209	39850;39851;39852	chr2:178582125;178582124;178582123	chr2:179446852;179446851;179446850
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-48
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.2406
• 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
D/G	None	None	0.963	N	0.689	0.581	0.467416895013	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
D/A	0.9512	likely_pathogenic	0.8383	pathogenic	-0.258	Destabilizing	0.978	D	0.71	prob.delet.	N	0.493716228	None	None	N
D/C	0.992	likely_pathogenic	0.9703	pathogenic	0.102	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
D/E	0.9482	likely_pathogenic	0.8635	pathogenic	-0.695	Destabilizing	0.963	D	0.495	neutral	N	0.493689775	None	None	N
D/F	0.995	likely_pathogenic	0.9843	pathogenic	-0.52	Destabilizing	0.968	D	0.783	deleterious	None	None	None	None	N
D/G	0.9232	likely_pathogenic	0.7948	pathogenic	-0.521	Destabilizing	0.963	D	0.689	prob.neutral	N	0.520912291	None	None	N
D/H	0.9656	likely_pathogenic	0.9011	pathogenic	-0.912	Destabilizing	0.994	D	0.799	deleterious	N	0.51093511	None	None	N
D/I	0.9897	likely_pathogenic	0.9551	pathogenic	0.398	Stabilizing	0.983	D	0.804	deleterious	None	None	None	None	N
D/K	0.9882	likely_pathogenic	0.9637	pathogenic	0.005	Stabilizing	0.983	D	0.799	deleterious	None	None	None	None	N
D/L	0.9854	likely_pathogenic	0.9537	pathogenic	0.398	Stabilizing	0.968	D	0.766	deleterious	None	None	None	None	N
D/M	0.994	likely_pathogenic	0.9773	pathogenic	0.851	Stabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
D/N	0.3538	ambiguous	0.1993	benign	-0.257	Destabilizing	0.989	D	0.745	deleterious	N	0.467965424	None	None	N
D/P	0.9912	likely_pathogenic	0.9789	pathogenic	0.204	Stabilizing	0.997	D	0.811	deleterious	None	None	None	None	N
D/Q	0.9862	likely_pathogenic	0.9535	pathogenic	-0.19	Destabilizing	0.992	D	0.784	deleterious	None	None	None	None	N
D/R	0.9884	likely_pathogenic	0.9636	pathogenic	-0.104	Destabilizing	0.992	D	0.822	deleterious	None	None	None	None	N
D/S	0.7385	likely_pathogenic	0.4835	ambiguous	-0.415	Destabilizing	0.983	D	0.743	deleterious	None	None	None	None	N
D/T	0.8659	likely_pathogenic	0.6551	pathogenic	-0.204	Destabilizing	0.992	D	0.794	deleterious	None	None	None	None	N
D/V	0.9724	likely_pathogenic	0.8963	pathogenic	0.204	Stabilizing	0.978	D	0.775	deleterious	N	0.519644843	None	None	N
D/W	0.9989	likely_pathogenic	0.9967	pathogenic	-0.544	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
D/Y	0.9602	likely_pathogenic	0.8822	pathogenic	-0.32	Destabilizing	0.085	N	0.557	neutral	D	0.53243318	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.