TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31224	93895;93896;93897	chr2:178547956;178547955;178547954	chr2:179412683;179412682;179412681
N2AB	29583	88972;88973;88974	chr2:178547956;178547955;178547954	chr2:179412683;179412682;179412681
N2A	28656	86191;86192;86193	chr2:178547956;178547955;178547954	chr2:179412683;179412682;179412681
N2B	22159	66700;66701;66702	chr2:178547956;178547955;178547954	chr2:179412683;179412682;179412681
Novex-1	22284	67075;67076;67077	chr2:178547956;178547955;178547954	chr2:179412683;179412682;179412681
Novex-2	22351	67276;67277;67278	chr2:178547956;178547955;178547954	chr2:179412683;179412682;179412681
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-151
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.4347
• 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
L/P	None	None	0.879	N	0.581	0.297	0.68047775509	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	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
L/A	0.3085	likely_benign	0.258	benign	-1.59	Destabilizing	0.404	N	0.443	neutral	None	None	None	None	I
L/C	0.4677	ambiguous	0.4025	ambiguous	-0.978	Destabilizing	0.991	D	0.509	neutral	None	None	None	None	I
L/D	0.7073	likely_pathogenic	0.651	pathogenic	-1.053	Destabilizing	0.826	D	0.571	neutral	None	None	None	None	I
L/E	0.3098	likely_benign	0.291	benign	-1.057	Destabilizing	0.826	D	0.54	neutral	None	None	None	None	I
L/F	0.1939	likely_benign	0.1519	benign	-1.144	Destabilizing	0.782	D	0.427	neutral	N	0.465019958	None	None	I
L/G	0.6339	likely_pathogenic	0.5705	pathogenic	-1.906	Destabilizing	0.826	D	0.532	neutral	None	None	None	None	I
L/H	0.2234	likely_benign	0.1808	benign	-1.215	Destabilizing	0.017	N	0.399	neutral	N	0.494649432	None	None	I
L/I	0.0889	likely_benign	0.0818	benign	-0.799	Destabilizing	0.007	N	0.245	neutral	N	0.451109298	None	None	I
L/K	0.2146	likely_benign	0.1948	benign	-1.139	Destabilizing	0.826	D	0.505	neutral	None	None	None	None	I
L/M	0.1029	likely_benign	0.0906	benign	-0.597	Destabilizing	0.826	D	0.452	neutral	None	None	None	None	I
L/N	0.3611	ambiguous	0.2963	benign	-0.943	Destabilizing	0.826	D	0.566	neutral	None	None	None	None	I
L/P	0.8859	likely_pathogenic	0.8889	pathogenic	-1.03	Destabilizing	0.879	D	0.581	neutral	N	0.428616441	None	None	I
L/Q	0.1235	likely_benign	0.1175	benign	-1.119	Destabilizing	0.826	D	0.547	neutral	None	None	None	None	I
L/R	0.1783	likely_benign	0.1631	benign	-0.572	Destabilizing	0.782	D	0.544	neutral	N	0.42507749	None	None	I
L/S	0.3631	ambiguous	0.2908	benign	-1.538	Destabilizing	0.404	N	0.488	neutral	None	None	None	None	I
L/T	0.172	likely_benign	0.1503	benign	-1.428	Destabilizing	0.018	N	0.248	neutral	None	None	None	None	I
L/V	0.0853	likely_benign	0.0805	benign	-1.03	Destabilizing	0.068	N	0.475	neutral	N	0.427059003	None	None	I
L/W	0.3221	likely_benign	0.2858	benign	-1.236	Destabilizing	0.991	D	0.618	neutral	None	None	None	None	I
L/Y	0.3559	ambiguous	0.2919	benign	-1.006	Destabilizing	0.826	D	0.484	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.