TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8254	24985;24986;24987	chr2:178718346;178718345;178718344	chr2:179583073;179583072;179583071
N2AB	7937	24034;24035;24036	chr2:178718346;178718345;178718344	chr2:179583073;179583072;179583071
N2A	7010	21253;21254;21255	chr2:178718346;178718345;178718344	chr2:179583073;179583072;179583071
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-67
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1048
• 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
C/G	None	None	0.959	N	0.746	0.466	0.85755753267	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
C/S	rs776063057	-1.772	0.476	N	0.548	0.226	0.670872402834	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
C/S	rs776063057	-1.772	0.476	N	0.548	0.226	0.670872402834	gnomAD-4.0.0	7.5276E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99609E-06	0	1.65667E-05

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
C/A	0.612	likely_pathogenic	0.5371	ambiguous	-1.992	Destabilizing	0.864	D	0.552	neutral	None	None	None	None	N
C/D	0.9617	likely_pathogenic	0.9429	pathogenic	-0.847	Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
C/E	0.9828	likely_pathogenic	0.9723	pathogenic	-0.691	Destabilizing	0.991	D	0.798	deleterious	None	None	None	None	N
C/F	0.7718	likely_pathogenic	0.6833	pathogenic	-1.222	Destabilizing	0.068	N	0.641	neutral	D	0.532701394	None	None	N
C/G	0.4443	ambiguous	0.355	ambiguous	-2.337	Highly Destabilizing	0.959	D	0.746	deleterious	N	0.521180504	None	None	N
C/H	0.9558	likely_pathogenic	0.9213	pathogenic	-2.284	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
C/I	0.8851	likely_pathogenic	0.8406	pathogenic	-1.075	Destabilizing	0.939	D	0.709	prob.delet.	None	None	None	None	N
C/K	0.9938	likely_pathogenic	0.9889	pathogenic	-1.281	Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
C/L	0.8574	likely_pathogenic	0.8008	pathogenic	-1.075	Destabilizing	0.864	D	0.682	prob.neutral	None	None	None	None	N
C/M	0.9023	likely_pathogenic	0.868	pathogenic	0.043	Stabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
C/N	0.9124	likely_pathogenic	0.8727	pathogenic	-1.465	Destabilizing	0.991	D	0.804	deleterious	None	None	None	None	N
C/P	0.9971	likely_pathogenic	0.9955	pathogenic	-1.356	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
C/Q	0.962	likely_pathogenic	0.9376	pathogenic	-1.252	Destabilizing	0.995	D	0.808	deleterious	None	None	None	None	N
C/R	0.9517	likely_pathogenic	0.9238	pathogenic	-1.24	Destabilizing	0.994	D	0.811	deleterious	N	0.492440733	None	None	N
C/S	0.3864	ambiguous	0.3125	benign	-2.001	Highly Destabilizing	0.476	N	0.548	neutral	N	0.492498214	None	None	N
C/T	0.5484	ambiguous	0.5212	ambiguous	-1.655	Destabilizing	0.939	D	0.71	prob.delet.	None	None	None	None	N
C/V	0.7786	likely_pathogenic	0.7189	pathogenic	-1.356	Destabilizing	0.293	N	0.447	neutral	None	None	None	None	N
C/W	0.9495	likely_pathogenic	0.9061	pathogenic	-1.302	Destabilizing	0.999	D	0.724	prob.delet.	N	0.521940973	None	None	N
C/Y	0.9195	likely_pathogenic	0.8656	pathogenic	-1.28	Destabilizing	0.976	D	0.776	deleterious	N	0.510077689	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.