TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31384	94375;94376;94377	chr2:178547476;178547475;178547474	chr2:179412203;179412202;179412201
N2AB	29743	89452;89453;89454	chr2:178547476;178547475;178547474	chr2:179412203;179412202;179412201
N2A	28816	86671;86672;86673	chr2:178547476;178547475;178547474	chr2:179412203;179412202;179412201
N2B	22319	67180;67181;67182	chr2:178547476;178547475;178547474	chr2:179412203;179412202;179412201
Novex-1	22444	67555;67556;67557	chr2:178547476;178547475;178547474	chr2:179412203;179412202;179412201
Novex-2	22511	67756;67757;67758	chr2:178547476;178547475;178547474	chr2:179412203;179412202;179412201
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-116
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1049
• 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
S/G	rs369254232	-3.168	0.549	N	0.693	0.219	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/G	rs369254232	-3.168	0.549	N	0.693	0.219	None	gnomAD-4.0.0	1.86045E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54415E-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
S/A	0.1155	likely_benign	0.1198	benign	-1.043	Destabilizing	0.127	N	0.54	neutral	None	None	None	None	N
S/C	0.061	likely_benign	0.065	benign	-1.141	Destabilizing	0.004	N	0.481	neutral	N	0.48384894	None	None	N
S/D	0.9407	likely_pathogenic	0.9412	pathogenic	-2.238	Highly Destabilizing	0.909	D	0.727	prob.delet.	None	None	None	None	N
S/E	0.9225	likely_pathogenic	0.9212	pathogenic	-2.053	Highly Destabilizing	0.909	D	0.736	prob.delet.	None	None	None	None	N
S/F	0.3189	likely_benign	0.3301	benign	-0.914	Destabilizing	0.85	D	0.691	prob.neutral	None	None	None	None	N
S/G	0.2016	likely_benign	0.2032	benign	-1.382	Destabilizing	0.549	D	0.693	prob.neutral	N	0.489966792	None	None	N
S/H	0.5915	likely_pathogenic	0.5797	pathogenic	-1.666	Destabilizing	0.992	D	0.7	prob.neutral	None	None	None	None	N
S/I	0.4611	ambiguous	0.468	ambiguous	-0.191	Destabilizing	0.379	N	0.681	prob.neutral	N	0.47580546	None	None	N
S/K	0.9179	likely_pathogenic	0.9217	pathogenic	-0.68	Destabilizing	0.766	D	0.731	prob.delet.	None	None	None	None	N
S/L	0.2352	likely_benign	0.2335	benign	-0.191	Destabilizing	0.25	N	0.705	prob.neutral	None	None	None	None	N
S/M	0.3093	likely_benign	0.3214	benign	-0.359	Destabilizing	0.127	N	0.636	neutral	None	None	None	None	N
S/N	0.5084	ambiguous	0.4993	ambiguous	-1.435	Destabilizing	0.883	D	0.725	prob.delet.	N	0.477938923	None	None	N
S/P	0.9946	likely_pathogenic	0.9944	pathogenic	-0.444	Destabilizing	0.972	D	0.738	prob.delet.	None	None	None	None	N
S/Q	0.7103	likely_pathogenic	0.7044	pathogenic	-1.239	Destabilizing	0.92	D	0.741	deleterious	None	None	None	None	N
S/R	0.7887	likely_pathogenic	0.7957	pathogenic	-0.919	Destabilizing	0.896	D	0.738	prob.delet.	N	0.396843244	None	None	N
S/T	0.202	likely_benign	0.2052	benign	-1.03	Destabilizing	0.549	D	0.67	neutral	N	0.478344333	None	None	N
S/V	0.4275	ambiguous	0.4152	ambiguous	-0.444	Destabilizing	0.447	N	0.689	prob.neutral	None	None	None	None	N
S/W	0.5883	likely_pathogenic	0.6048	pathogenic	-1.224	Destabilizing	0.992	D	0.725	prob.delet.	None	None	None	None	N
S/Y	0.3408	ambiguous	0.342	ambiguous	-0.781	Destabilizing	0.972	D	0.696	prob.neutral	None	None	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.