TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6092	18499;18500;18501	chr2:178730126;178730125;178730124	chr2:179594853;179594852;179594851
N2AB	5775	17548;17549;17550	chr2:178730126;178730125;178730124	chr2:179594853;179594852;179594851
N2A	4848	14767;14768;14769	chr2:178730126;178730125;178730124	chr2:179594853;179594852;179594851
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-44
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6041
• 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/A	rs1257068599	-0.447	None	N	0.102	0.053	0.110078149338	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	1E-04	0	None	0	None	0	0	0
T/A	rs1257068599	-0.447	None	N	0.102	0.053	0.110078149338	gnomAD-4.0.0	1.5929E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02718E-05
T/R	None	None	0.171	N	0.481	0.122	0.302459207581	gnomAD-4.0.0	1.59304E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02755E-05

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	0.0823	likely_benign	0.0832	benign	-0.528	Destabilizing	None	N	0.102	neutral	N	0.448363435	None	None	I
T/C	0.4388	ambiguous	0.4175	ambiguous	-0.262	Destabilizing	0.628	D	0.487	neutral	None	None	None	None	I
T/D	0.3753	ambiguous	0.3516	ambiguous	-0.071	Destabilizing	0.072	N	0.475	neutral	None	None	None	None	I
T/E	0.2946	likely_benign	0.2744	benign	-0.153	Destabilizing	0.072	N	0.408	neutral	None	None	None	None	I
T/F	0.1717	likely_benign	0.1712	benign	-0.99	Destabilizing	0.12	N	0.545	neutral	None	None	None	None	I
T/G	0.2671	likely_benign	0.2644	benign	-0.662	Destabilizing	0.016	N	0.496	neutral	None	None	None	None	I
T/H	0.2249	likely_benign	0.2204	benign	-0.986	Destabilizing	0.676	D	0.538	neutral	None	None	None	None	I
T/I	0.1259	likely_benign	0.1139	benign	-0.288	Destabilizing	None	N	0.269	neutral	N	0.452713249	None	None	I
T/K	0.189	likely_benign	0.1722	benign	-0.468	Destabilizing	0.029	N	0.409	neutral	N	0.401780209	None	None	I
T/L	0.0961	likely_benign	0.0895	benign	-0.288	Destabilizing	None	N	0.203	neutral	None	None	None	None	I
T/M	0.0787	likely_benign	0.0789	benign	0.064	Stabilizing	0.12	N	0.486	neutral	None	None	None	None	I
T/N	0.106	likely_benign	0.1039	benign	-0.202	Destabilizing	0.038	N	0.375	neutral	None	None	None	None	I
T/P	0.2876	likely_benign	0.304	benign	-0.34	Destabilizing	0.295	N	0.469	neutral	N	0.505603584	None	None	I
T/Q	0.207	likely_benign	0.2036	benign	-0.512	Destabilizing	0.214	N	0.494	neutral	None	None	None	None	I
T/R	0.1709	likely_benign	0.1601	benign	-0.124	Destabilizing	0.171	N	0.481	neutral	N	0.455444123	None	None	I
T/S	0.0944	likely_benign	0.0972	benign	-0.424	Destabilizing	None	N	0.112	neutral	N	0.375943189	None	None	I
T/V	0.1043	likely_benign	0.1012	benign	-0.34	Destabilizing	0.006	N	0.329	neutral	None	None	None	None	I
T/W	0.5159	ambiguous	0.5214	ambiguous	-0.94	Destabilizing	0.864	D	0.563	neutral	None	None	None	None	I
T/Y	0.2307	likely_benign	0.2279	benign	-0.687	Destabilizing	0.356	N	0.556	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.