TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8161	24706;24707;24708	chr2:178718719;178718718;178718717	chr2:179583446;179583445;179583444
N2AB	7844	23755;23756;23757	chr2:178718719;178718718;178718717	chr2:179583446;179583445;179583444
N2A	6917	20974;20975;20976	chr2:178718719;178718718;178718717	chr2:179583446;179583445;179583444
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-66
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1032
• 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/Y	rs372143487	-1.34	0.994	N	0.822	0.441	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
C/Y	rs372143487	-1.34	0.994	N	0.822	0.441	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
C/Y	rs372143487	-1.34	0.994	N	0.822	0.441	None	gnomAD-4.0.0	1.48737E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.94964E-05	1.09803E-05	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	0.5145	ambiguous	0.5647	pathogenic	-1.659	Destabilizing	0.982	D	0.619	neutral	None	None	None	None	N
C/D	0.8805	likely_pathogenic	0.9021	pathogenic	0.163	Stabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
C/E	0.9309	likely_pathogenic	0.9376	pathogenic	0.251	Stabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
C/F	0.3375	likely_benign	0.3897	ambiguous	-1.192	Destabilizing	0.994	D	0.823	deleterious	D	0.524801355	None	None	N
C/G	0.3289	likely_benign	0.3847	ambiguous	-1.943	Destabilizing	0.997	D	0.83	deleterious	N	0.504228338	None	None	N
C/H	0.7153	likely_pathogenic	0.7625	pathogenic	-1.999	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
C/I	0.6162	likely_pathogenic	0.692	pathogenic	-0.941	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
C/K	0.9141	likely_pathogenic	0.9222	pathogenic	-0.481	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
C/L	0.6347	likely_pathogenic	0.6814	pathogenic	-0.941	Destabilizing	0.985	D	0.693	prob.neutral	None	None	None	None	N
C/M	0.7539	likely_pathogenic	0.8	pathogenic	-0.24	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
C/N	0.7547	likely_pathogenic	0.7915	pathogenic	-0.419	Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
C/P	0.9921	likely_pathogenic	0.9935	pathogenic	-1.155	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
C/Q	0.8008	likely_pathogenic	0.8206	pathogenic	-0.343	Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
C/R	0.6467	likely_pathogenic	0.6618	pathogenic	-0.471	Destabilizing	0.999	D	0.876	deleterious	N	0.490959476	None	None	N
C/S	0.331	likely_benign	0.3861	ambiguous	-0.996	Destabilizing	0.999	D	0.793	deleterious	N	0.52158897	None	None	N
C/T	0.5221	ambiguous	0.5851	pathogenic	-0.719	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
C/V	0.5185	ambiguous	0.5778	pathogenic	-1.155	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	N
C/W	0.7323	likely_pathogenic	0.7939	pathogenic	-1.131	Destabilizing	0.265	N	0.625	neutral	N	0.514205519	None	None	N
C/Y	0.5692	likely_pathogenic	0.611	pathogenic	-1.091	Destabilizing	0.994	D	0.822	deleterious	N	0.490985929	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.