TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9009	27250;27251;27252	chr2:178713109;178713108;178713107	chr2:179577836;179577835;179577834
N2AB	8692	26299;26300;26301	chr2:178713109;178713108;178713107	chr2:179577836;179577835;179577834
N2A	7765	23518;23519;23520	chr2:178713109;178713108;178713107	chr2:179577836;179577835;179577834
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-75
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1343
• 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	rs369287578	-2.722	0.999	N	0.797	0.387	0.853887960626	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
C/G	rs369287578	-2.722	0.999	N	0.797	0.387	0.853887960626	gnomAD-4.0.0	1.59181E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85919E-06	0	0
C/R	rs369287578	-1.172	0.999	N	0.847	0.482	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	8.89E-06	0
C/R	rs369287578	-1.172	0.999	N	0.847	0.482	None	gnomAD-4.0.0	1.59181E-06	None	None	None	None	N	None	0	2.28718E-05	None	0	0	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
C/A	0.5454	ambiguous	0.5357	ambiguous	-1.957	Destabilizing	0.994	D	0.563	neutral	None	None	None	None	N
C/D	0.8937	likely_pathogenic	0.9078	pathogenic	-0.857	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
C/E	0.9689	likely_pathogenic	0.9747	pathogenic	-0.726	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
C/F	0.5986	likely_pathogenic	0.652	pathogenic	-1.215	Destabilizing	0.999	D	0.773	deleterious	N	0.513433633	None	None	N
C/G	0.3389	likely_benign	0.3478	ambiguous	-2.286	Highly Destabilizing	0.999	D	0.797	deleterious	N	0.509123892	None	None	N
C/H	0.9066	likely_pathogenic	0.9231	pathogenic	-2.268	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
C/I	0.7072	likely_pathogenic	0.763	pathogenic	-1.091	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
C/K	0.9818	likely_pathogenic	0.9865	pathogenic	-1.311	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
C/L	0.7532	likely_pathogenic	0.7807	pathogenic	-1.091	Destabilizing	0.997	D	0.649	neutral	None	None	None	None	N
C/M	0.7868	likely_pathogenic	0.8064	pathogenic	-0.013	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
C/N	0.7514	likely_pathogenic	0.7808	pathogenic	-1.37	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
C/P	0.9971	likely_pathogenic	0.9977	pathogenic	-1.355	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
C/Q	0.9368	likely_pathogenic	0.9446	pathogenic	-1.234	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
C/R	0.9114	likely_pathogenic	0.9294	pathogenic	-1.198	Destabilizing	0.999	D	0.847	deleterious	N	0.504563434	None	None	N
C/S	0.3092	likely_benign	0.3234	benign	-1.905	Destabilizing	0.997	D	0.692	prob.neutral	N	0.410882482	None	None	N
C/T	0.3505	ambiguous	0.3496	ambiguous	-1.594	Destabilizing	0.997	D	0.709	prob.delet.	None	None	None	None	N
C/V	0.5501	ambiguous	0.5862	pathogenic	-1.355	Destabilizing	0.997	D	0.661	neutral	None	None	None	None	N
C/W	0.9035	likely_pathogenic	0.9248	pathogenic	-1.262	Destabilizing	1.0	D	0.766	deleterious	N	0.517994091	None	None	N
C/Y	0.763	likely_pathogenic	0.8164	pathogenic	-1.253	Destabilizing	0.999	D	0.791	deleterious	D	0.532462111	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.