TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20849	62770;62771;62772	chr2:178589180;178589179;178589178	chr2:179453907;179453906;179453905
N2AB	19208	57847;57848;57849	chr2:178589180;178589179;178589178	chr2:179453907;179453906;179453905
N2A	18281	55066;55067;55068	chr2:178589180;178589179;178589178	chr2:179453907;179453906;179453905
N2B	11784	35575;35576;35577	chr2:178589180;178589179;178589178	chr2:179453907;179453906;179453905
Novex-1	11909	35950;35951;35952	chr2:178589180;178589179;178589178	chr2:179453907;179453906;179453905
Novex-2	11976	36151;36152;36153	chr2:178589180;178589179;178589178	chr2:179453907;179453906;179453905
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-122
• Domain position: 81
• Structural Position: 162
• Q(SASA): 0.7672
• 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
T/M	rs372685222	-0.051	0.537	N	0.311	0.11	None	gnomAD-2.1.1	3.57E-05	None	None	None	None	I	None	2.06629E-04	0	None	0	1.54735E-04	None	0	None	0	1.56E-05	0
T/M	rs372685222	-0.051	0.537	N	0.311	0.11	None	gnomAD-3.1.2	8.55E-05	None	None	None	None	I	None	1.68968E-04	6.56E-05	0	0	1.94024E-04	None	0	0	5.88E-05	0	0
T/M	rs372685222	-0.051	0.537	N	0.311	0.11	None	gnomAD-4.0.0	2.47935E-05	None	None	None	None	I	None	2.00304E-04	1.66795E-05	None	0	6.70301E-05	None	0	0	1.78023E-05	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
T/A	0.0541	likely_benign	0.0565	benign	-0.195	Destabilizing	None	N	0.094	neutral	N	0.446765924	None	None	I
T/C	0.3562	ambiguous	0.4216	ambiguous	-0.371	Destabilizing	0.628	D	0.312	neutral	None	None	None	None	I
T/D	0.316	likely_benign	0.3456	ambiguous	-0.046	Destabilizing	0.072	N	0.3	neutral	None	None	None	None	I
T/E	0.2472	likely_benign	0.2837	benign	-0.141	Destabilizing	0.072	N	0.309	neutral	None	None	None	None	I
T/F	0.2593	likely_benign	0.2829	benign	-0.858	Destabilizing	0.214	N	0.342	neutral	None	None	None	None	I
T/G	0.1564	likely_benign	0.1673	benign	-0.25	Destabilizing	0.016	N	0.349	neutral	None	None	None	None	I
T/H	0.2234	likely_benign	0.2464	benign	-0.451	Destabilizing	0.864	D	0.325	neutral	None	None	None	None	I
T/I	0.1221	likely_benign	0.1435	benign	-0.172	Destabilizing	None	N	0.283	neutral	None	None	None	None	I
T/K	0.1945	likely_benign	0.2129	benign	-0.326	Destabilizing	0.13	N	0.311	neutral	N	0.455230692	None	None	I
T/L	0.081	likely_benign	0.0846	benign	-0.172	Destabilizing	None	N	0.141	neutral	None	None	None	None	I
T/M	0.0837	likely_benign	0.0917	benign	-0.136	Destabilizing	0.537	D	0.311	neutral	N	0.474819317	None	None	I
T/N	0.0989	likely_benign	0.1094	benign	-0.147	Destabilizing	0.072	N	0.251	neutral	None	None	None	None	I
T/P	0.0696	likely_benign	0.0816	benign	-0.156	Destabilizing	None	N	0.119	neutral	N	0.445573846	None	None	I
T/Q	0.1729	likely_benign	0.2008	benign	-0.363	Destabilizing	0.356	N	0.309	neutral	None	None	None	None	I
T/R	0.1949	likely_benign	0.2038	benign	-0.046	Destabilizing	0.515	D	0.317	neutral	N	0.465255684	None	None	I
T/S	0.0773	likely_benign	0.0799	benign	-0.296	Destabilizing	0.002	N	0.163	neutral	N	0.390755139	None	None	I
T/V	0.0954	likely_benign	0.1081	benign	-0.156	Destabilizing	0.006	N	0.303	neutral	None	None	None	None	I
T/W	0.6525	likely_pathogenic	0.6781	pathogenic	-0.94	Destabilizing	0.864	D	0.347	neutral	None	None	None	None	I
T/Y	0.3037	likely_benign	0.3335	benign	-0.623	Destabilizing	0.356	N	0.332	neutral	None	None	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.