TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27665	83218;83219;83220	chr2:178563139;178563138;178563137	chr2:179427866;179427865;179427864
N2AB	26024	78295;78296;78297	chr2:178563139;178563138;178563137	chr2:179427866;179427865;179427864
N2A	25097	75514;75515;75516	chr2:178563139;178563138;178563137	chr2:179427866;179427865;179427864
N2B	18600	56023;56024;56025	chr2:178563139;178563138;178563137	chr2:179427866;179427865;179427864
Novex-1	18725	56398;56399;56400	chr2:178563139;178563138;178563137	chr2:179427866;179427865;179427864
Novex-2	18792	56599;56600;56601	chr2:178563139;178563138;178563137	chr2:179427866;179427865;179427864
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-89
• Domain position: 96
• Structural Position: 129
• Q(SASA): 0.3428
• 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
V/F	None	None	None	N	0.354	0.084	0.300449992093	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
V/G	rs1704304364	None	0.013	N	0.461	0.189	0.436132833422	gnomAD-4.0.0	6.84237E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-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
V/A	0.1096	likely_benign	0.1061	benign	-1.298	Destabilizing	None	N	0.134	neutral	N	0.519356741	None	None	N
V/C	0.5492	ambiguous	0.5459	ambiguous	-1.03	Destabilizing	0.204	N	0.309	neutral	None	None	None	None	N
V/D	0.3737	ambiguous	0.3434	ambiguous	-1.162	Destabilizing	0.026	N	0.58	neutral	N	0.490705986	None	None	N
V/E	0.2303	likely_benign	0.2135	benign	-1.211	Destabilizing	0.035	N	0.504	neutral	None	None	None	None	N
V/F	0.1133	likely_benign	0.1134	benign	-1.213	Destabilizing	None	N	0.354	neutral	N	0.520396891	None	None	N
V/G	0.2071	likely_benign	0.1891	benign	-1.552	Destabilizing	0.013	N	0.461	neutral	N	0.490452496	None	None	N
V/H	0.3601	ambiguous	0.3498	ambiguous	-1.018	Destabilizing	0.204	N	0.427	neutral	None	None	None	None	N
V/I	0.0619	likely_benign	0.0678	benign	-0.725	Destabilizing	None	N	0.055	neutral	N	0.430852322	None	None	N
V/K	0.1718	likely_benign	0.1576	benign	-0.983	Destabilizing	0.018	N	0.407	neutral	None	None	None	None	N
V/L	0.0863	likely_benign	0.0951	benign	-0.725	Destabilizing	None	N	0.065	neutral	N	0.462500594	None	None	N
V/M	0.0836	likely_benign	0.0942	benign	-0.552	Destabilizing	0.112	N	0.363	neutral	None	None	None	None	N
V/N	0.2126	likely_benign	0.2121	benign	-0.778	Destabilizing	0.035	N	0.604	neutral	None	None	None	None	N
V/P	0.3115	likely_benign	0.2936	benign	-0.88	Destabilizing	0.112	N	0.595	neutral	None	None	None	None	N
V/Q	0.1965	likely_benign	0.1824	benign	-1.042	Destabilizing	0.112	N	0.57	neutral	None	None	None	None	N
V/R	0.1704	likely_benign	0.1495	benign	-0.399	Destabilizing	None	N	0.4	neutral	None	None	None	None	N
V/S	0.1562	likely_benign	0.148	benign	-1.272	Destabilizing	0.007	N	0.35	neutral	None	None	None	None	N
V/T	0.0999	likely_benign	0.1044	benign	-1.217	Destabilizing	None	N	0.178	neutral	None	None	None	None	N
V/W	0.6003	likely_pathogenic	0.5953	pathogenic	-1.305	Destabilizing	0.747	D	0.449	neutral	None	None	None	None	N
V/Y	0.3754	ambiguous	0.3677	ambiguous	-1.012	Destabilizing	0.018	N	0.48	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.