TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32858	98797;98798;98799	chr2:178539493;178539492;178539491	chr2:179404220;179404219;179404218
N2AB	31217	93874;93875;93876	chr2:178539493;178539492;178539491	chr2:179404220;179404219;179404218
N2A	30290	91093;91094;91095	chr2:178539493;178539492;178539491	chr2:179404220;179404219;179404218
N2B	23793	71602;71603;71604	chr2:178539493;178539492;178539491	chr2:179404220;179404219;179404218
Novex-1	23918	71977;71978;71979	chr2:178539493;178539492;178539491	chr2:179404220;179404219;179404218
Novex-2	23985	72178;72179;72180	chr2:178539493;178539492;178539491	chr2:179404220;179404219;179404218
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-127
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.6402
• 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
K/T	rs1322355821	None	0.978	N	0.714	0.378	0.34854441366	gnomAD-4.0.0	3.18228E-06	None	None	None	None	N	None	0	0	None	0	5.54539E-05	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
K/A	0.7178	likely_pathogenic	0.6155	pathogenic	-0.02	Destabilizing	0.944	D	0.598	neutral	None	None	None	None	N
K/C	0.9099	likely_pathogenic	0.8571	pathogenic	-0.382	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
K/D	0.8391	likely_pathogenic	0.793	pathogenic	0.262	Stabilizing	0.992	D	0.749	deleterious	None	None	None	None	N
K/E	0.4814	ambiguous	0.3979	ambiguous	0.284	Stabilizing	0.928	D	0.554	neutral	N	0.465761825	None	None	N
K/F	0.9527	likely_pathogenic	0.9215	pathogenic	-0.203	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/G	0.7635	likely_pathogenic	0.6763	pathogenic	-0.22	Destabilizing	0.983	D	0.613	neutral	None	None	None	None	N
K/H	0.5526	ambiguous	0.4624	ambiguous	-0.372	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
K/I	0.8118	likely_pathogenic	0.7304	pathogenic	0.427	Stabilizing	0.989	D	0.733	prob.delet.	N	0.503648209	None	None	N
K/L	0.726	likely_pathogenic	0.6306	pathogenic	0.427	Stabilizing	0.983	D	0.613	neutral	None	None	None	None	N
K/M	0.627	likely_pathogenic	0.5259	ambiguous	0.105	Stabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	N
K/N	0.7248	likely_pathogenic	0.6439	pathogenic	0.109	Stabilizing	0.978	D	0.691	prob.neutral	N	0.490332195	None	None	N
K/P	0.7973	likely_pathogenic	0.7116	pathogenic	0.306	Stabilizing	0.997	D	0.757	deleterious	None	None	None	None	N
K/Q	0.303	likely_benign	0.2362	benign	-0.01	Destabilizing	0.978	D	0.686	prob.neutral	N	0.474613381	None	None	N
K/R	0.1045	likely_benign	0.088	benign	-0.013	Destabilizing	0.085	N	0.295	neutral	N	0.47030364	None	None	N
K/S	0.7089	likely_pathogenic	0.63	pathogenic	-0.421	Destabilizing	0.944	D	0.613	neutral	None	None	None	None	N
K/T	0.4242	ambiguous	0.3475	ambiguous	-0.243	Destabilizing	0.978	D	0.714	prob.delet.	N	0.417506518	None	None	N
K/V	0.7578	likely_pathogenic	0.6743	pathogenic	0.306	Stabilizing	0.992	D	0.709	prob.delet.	None	None	None	None	N
K/W	0.92	likely_pathogenic	0.8663	pathogenic	-0.222	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
K/Y	0.8734	likely_pathogenic	0.8129	pathogenic	0.137	Stabilizing	0.997	D	0.727	prob.delet.	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.