TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7291	22096;22097;22098	chr2:178723136;178723135;178723134	chr2:179587863;179587862;179587861
N2AB	6974	21145;21146;21147	chr2:178723136;178723135;178723134	chr2:179587863;179587862;179587861
N2A	6047	18364;18365;18366	chr2:178723136;178723135;178723134	chr2:179587863;179587862;179587861
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-57
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.7112
• 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
N/K	None	None	0.062	N	0.287	0.083	0.115124310173	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1641	likely_benign	0.1581	benign	-0.442	Destabilizing	0.035	N	0.352	neutral	None	None	None	None	N
N/C	0.2434	likely_benign	0.2211	benign	0.385	Stabilizing	0.824	D	0.355	neutral	None	None	None	None	N
N/D	0.0803	likely_benign	0.0785	benign	-0.087	Destabilizing	None	N	0.139	neutral	N	0.485800662	None	None	N
N/E	0.2229	likely_benign	0.2017	benign	-0.135	Destabilizing	0.035	N	0.321	neutral	None	None	None	None	N
N/F	0.3888	ambiguous	0.3758	ambiguous	-0.936	Destabilizing	0.555	D	0.383	neutral	None	None	None	None	N
N/G	0.1671	likely_benign	0.1757	benign	-0.584	Destabilizing	0.035	N	0.376	neutral	None	None	None	None	N
N/H	0.0791	likely_benign	0.0789	benign	-0.743	Destabilizing	0.484	N	0.333	neutral	N	0.509411027	None	None	N
N/I	0.2578	likely_benign	0.2176	benign	-0.157	Destabilizing	0.317	N	0.399	neutral	N	0.508833699	None	None	N
N/K	0.191	likely_benign	0.1756	benign	0.199	Stabilizing	0.062	N	0.287	neutral	N	0.499153961	None	None	N
N/L	0.2124	likely_benign	0.1956	benign	-0.157	Destabilizing	0.081	N	0.406	neutral	None	None	None	None	N
N/M	0.3192	likely_benign	0.3036	benign	0.439	Stabilizing	0.935	D	0.341	neutral	None	None	None	None	N
N/P	0.5037	ambiguous	0.4443	ambiguous	-0.228	Destabilizing	0.38	N	0.381	neutral	None	None	None	None	N
N/Q	0.2029	likely_benign	0.1953	benign	-0.358	Destabilizing	0.38	N	0.326	neutral	None	None	None	None	N
N/R	0.2046	likely_benign	0.1915	benign	0.291	Stabilizing	0.149	N	0.351	neutral	None	None	None	None	N
N/S	0.0728	likely_benign	0.0751	benign	-0.052	Destabilizing	None	N	0.091	neutral	N	0.464233311	None	None	N
N/T	0.1289	likely_benign	0.1118	benign	0.035	Stabilizing	None	N	0.153	neutral	N	0.504831927	None	None	N
N/V	0.2547	likely_benign	0.2148	benign	-0.228	Destabilizing	0.081	N	0.436	neutral	None	None	None	None	N
N/W	0.6256	likely_pathogenic	0.6119	pathogenic	-0.903	Destabilizing	0.935	D	0.5	neutral	None	None	None	None	N
N/Y	0.1226	likely_benign	0.1183	benign	-0.628	Destabilizing	0.484	N	0.359	neutral	N	0.50832672	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.