TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27855	83788;83789;83790	chr2:178562569;178562568;178562567	chr2:179427296;179427295;179427294
N2AB	26214	78865;78866;78867	chr2:178562569;178562568;178562567	chr2:179427296;179427295;179427294
N2A	25287	76084;76085;76086	chr2:178562569;178562568;178562567	chr2:179427296;179427295;179427294
N2B	18790	56593;56594;56595	chr2:178562569;178562568;178562567	chr2:179427296;179427295;179427294
Novex-1	18915	56968;56969;56970	chr2:178562569;178562568;178562567	chr2:179427296;179427295;179427294
Novex-2	18982	57169;57170;57171	chr2:178562569;178562568;178562567	chr2:179427296;179427295;179427294
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: Fn3-90
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.7526
• 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/I	rs1268315067	0.101	0.026	N	0.519	0.044	0.18274738541	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
T/I	rs1268315067	0.101	0.026	N	0.519	0.044	0.18274738541	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1268315067	0.101	0.026	N	0.519	0.044	0.18274738541	gnomAD-4.0.0	1.8624E-06	None	None	None	None	I	None	4.01263E-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
T/A	0.0538	likely_benign	0.0559	benign	-0.181	Destabilizing	None	N	0.076	neutral	N	0.444479688	None	None	I
T/C	0.245	likely_benign	0.2571	benign	-0.426	Destabilizing	0.492	N	0.388	neutral	None	None	None	None	I
T/D	0.2152	likely_benign	0.2132	benign	0.046	Stabilizing	0.018	N	0.461	neutral	None	None	None	None	I
T/E	0.1711	likely_benign	0.1715	benign	-0.037	Destabilizing	0.018	N	0.469	neutral	None	None	None	None	I
T/F	0.1564	likely_benign	0.1668	benign	-0.849	Destabilizing	0.204	N	0.58	neutral	None	None	None	None	I
T/G	0.1079	likely_benign	0.1093	benign	-0.245	Destabilizing	0.007	N	0.418	neutral	None	None	None	None	I
T/H	0.1726	likely_benign	0.178	benign	-0.343	Destabilizing	0.204	N	0.469	neutral	None	None	None	None	I
T/I	0.0802	likely_benign	0.0856	benign	-0.136	Destabilizing	0.026	N	0.519	neutral	N	0.513395482	None	None	I
T/K	0.1086	likely_benign	0.1132	benign	-0.276	Destabilizing	None	N	0.192	neutral	N	0.44282625	None	None	I
T/L	0.0575	likely_benign	0.0594	benign	-0.136	Destabilizing	0.007	N	0.459	neutral	None	None	None	None	I
T/M	0.0673	likely_benign	0.071	benign	-0.268	Destabilizing	0.204	N	0.405	neutral	None	None	None	None	I
T/N	0.0805	likely_benign	0.0828	benign	-0.129	Destabilizing	0.018	N	0.274	neutral	None	None	None	None	I
T/P	0.0646	likely_benign	0.0662	benign	-0.127	Destabilizing	None	N	0.115	neutral	N	0.467953981	None	None	I
T/Q	0.1289	likely_benign	0.1337	benign	-0.304	Destabilizing	0.06	N	0.519	neutral	None	None	None	None	I
T/R	0.1101	likely_benign	0.1175	benign	0.028	Stabilizing	0.013	N	0.513	neutral	N	0.467401858	None	None	I
T/S	0.0735	likely_benign	0.0739	benign	-0.285	Destabilizing	None	N	0.073	neutral	N	0.39099192	None	None	I
T/V	0.0675	likely_benign	0.072	benign	-0.127	Destabilizing	0.018	N	0.294	neutral	None	None	None	None	I
T/W	0.4361	ambiguous	0.4545	ambiguous	-0.952	Destabilizing	0.747	D	0.525	neutral	None	None	None	None	I
T/Y	0.2112	likely_benign	0.218	benign	-0.62	Destabilizing	0.204	N	0.554	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.