TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5806	17641;17642;17643	chr2:178731350;178731349;178731348	chr2:179596077;179596076;179596075
N2AB	5489	16690;16691;16692	chr2:178731350;178731349;178731348	chr2:179596077;179596076;179596075
N2A	4562	13909;13910;13911	chr2:178731350;178731349;178731348	chr2:179596077;179596076;179596075
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-41
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1775
• 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
N/K	rs990308126	None	1.0	D	0.742	0.497	0.247872288689	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
N/K	rs990308126	None	1.0	D	0.742	0.497	0.247872288689	gnomAD-4.0.0	7.68732E-06	None	None	None	None	I	None	0	1.69509E-05	None	0	0	None	0	0	7.1794E-06	0	5.68861E-05
N/S	None	None	0.999	N	0.594	0.524	0.325263233342	gnomAD-4.0.0	4.1054E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39692E-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
N/A	0.9976	likely_pathogenic	0.9962	pathogenic	-0.668	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
N/C	0.9915	likely_pathogenic	0.9862	pathogenic	-0.118	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
N/D	0.9798	likely_pathogenic	0.9732	pathogenic	-1.442	Destabilizing	0.999	D	0.63	neutral	D	0.525431741	None	None	I
N/E	0.9984	likely_pathogenic	0.9979	pathogenic	-1.357	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
N/F	0.9995	likely_pathogenic	0.9994	pathogenic	-0.616	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
N/G	0.9868	likely_pathogenic	0.9794	pathogenic	-0.973	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	I
N/H	0.9906	likely_pathogenic	0.9874	pathogenic	-0.855	Destabilizing	1.0	D	0.741	deleterious	D	0.526699189	None	None	I
N/I	0.9952	likely_pathogenic	0.9946	pathogenic	0.097	Stabilizing	1.0	D	0.717	prob.delet.	D	0.526952678	None	None	I
N/K	0.9987	likely_pathogenic	0.9985	pathogenic	-0.262	Destabilizing	1.0	D	0.742	deleterious	D	0.52619221	None	None	I
N/L	0.992	likely_pathogenic	0.9911	pathogenic	0.097	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
N/M	0.9939	likely_pathogenic	0.9929	pathogenic	0.615	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
N/P	0.9989	likely_pathogenic	0.9987	pathogenic	-0.129	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
N/Q	0.999	likely_pathogenic	0.9987	pathogenic	-1.096	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
N/R	0.9984	likely_pathogenic	0.9983	pathogenic	-0.192	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
N/S	0.9144	likely_pathogenic	0.8794	pathogenic	-0.862	Destabilizing	0.999	D	0.594	neutral	N	0.494957223	None	None	I
N/T	0.9687	likely_pathogenic	0.9585	pathogenic	-0.614	Destabilizing	0.999	D	0.717	prob.delet.	N	0.514328925	None	None	I
N/V	0.9949	likely_pathogenic	0.9942	pathogenic	-0.129	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
N/W	0.9997	likely_pathogenic	0.9997	pathogenic	-0.461	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
N/Y	0.9926	likely_pathogenic	0.992	pathogenic	-0.162	Destabilizing	1.0	D	0.739	prob.delet.	D	0.526699189	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.