TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20914	62965;62966;62967	chr2:178588985;178588984;178588983	chr2:179453712;179453711;179453710
N2AB	19273	58042;58043;58044	chr2:178588985;178588984;178588983	chr2:179453712;179453711;179453710
N2A	18346	55261;55262;55263	chr2:178588985;178588984;178588983	chr2:179453712;179453711;179453710
N2B	11849	35770;35771;35772	chr2:178588985;178588984;178588983	chr2:179453712;179453711;179453710
Novex-1	11974	36145;36146;36147	chr2:178588985;178588984;178588983	chr2:179453712;179453711;179453710
Novex-2	12041	36346;36347;36348	chr2:178588985;178588984;178588983	chr2:179453712;179453711;179453710
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: Fn3-39
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.3436
• 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
Y/S	rs1456081196	-1.543	0.908	N	0.745	0.298	0.648932385495	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
Y/S	rs1456081196	-1.543	0.908	N	0.745	0.298	0.648932385495	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/S	rs1456081196	-1.543	0.908	N	0.745	0.298	0.648932385495	gnomAD-4.0.0	2.56736E-06	None	None	None	None	I	None	1.69136E-05	0	None	0	2.44236E-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
Y/A	0.5802	likely_pathogenic	0.5758	pathogenic	-1.651	Destabilizing	0.648	D	0.655	neutral	None	None	None	None	I
Y/C	0.1422	likely_benign	0.1457	benign	-0.712	Destabilizing	0.991	D	0.747	deleterious	N	0.393344366	None	None	I
Y/D	0.7888	likely_pathogenic	0.8036	pathogenic	0.255	Stabilizing	0.968	D	0.777	deleterious	N	0.475074741	None	None	I
Y/E	0.9126	likely_pathogenic	0.9145	pathogenic	0.324	Stabilizing	0.929	D	0.751	deleterious	None	None	None	None	I
Y/F	0.0658	likely_benign	0.058	benign	-0.593	Destabilizing	0.004	N	0.375	neutral	N	0.415333004	None	None	I
Y/G	0.7691	likely_pathogenic	0.7738	pathogenic	-1.946	Destabilizing	0.929	D	0.756	deleterious	None	None	None	None	I
Y/H	0.2919	likely_benign	0.2953	benign	-0.497	Destabilizing	0.908	D	0.691	prob.neutral	N	0.416162511	None	None	I
Y/I	0.4179	ambiguous	0.3865	ambiguous	-0.797	Destabilizing	0.764	D	0.711	prob.delet.	None	None	None	None	I
Y/K	0.9265	likely_pathogenic	0.9266	pathogenic	-0.696	Destabilizing	0.929	D	0.755	deleterious	None	None	None	None	I
Y/L	0.5596	ambiguous	0.5664	pathogenic	-0.797	Destabilizing	0.48	N	0.523	neutral	None	None	None	None	I
Y/M	0.6748	likely_pathogenic	0.6572	pathogenic	-0.64	Destabilizing	0.98	D	0.775	deleterious	None	None	None	None	I
Y/N	0.4968	ambiguous	0.5056	ambiguous	-0.998	Destabilizing	0.968	D	0.766	deleterious	N	0.486291812	None	None	I
Y/P	0.9601	likely_pathogenic	0.9616	pathogenic	-1.071	Destabilizing	0.976	D	0.776	deleterious	None	None	None	None	I
Y/Q	0.7848	likely_pathogenic	0.7754	pathogenic	-0.863	Destabilizing	0.976	D	0.787	deleterious	None	None	None	None	I
Y/R	0.8329	likely_pathogenic	0.8308	pathogenic	-0.398	Destabilizing	0.929	D	0.766	deleterious	None	None	None	None	I
Y/S	0.3775	ambiguous	0.3829	ambiguous	-1.59	Destabilizing	0.908	D	0.745	deleterious	N	0.442231604	None	None	I
Y/T	0.5931	likely_pathogenic	0.5834	pathogenic	-1.421	Destabilizing	0.929	D	0.751	deleterious	None	None	None	None	I
Y/V	0.2976	likely_benign	0.2785	benign	-1.071	Destabilizing	0.48	N	0.661	neutral	None	None	None	None	I
Y/W	0.3708	ambiguous	0.3902	ambiguous	-0.34	Destabilizing	0.98	D	0.685	prob.neutral	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.