TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27634	83125;83126;83127	chr2:178563232;178563231;178563230	chr2:179427959;179427958;179427957
N2AB	25993	78202;78203;78204	chr2:178563232;178563231;178563230	chr2:179427959;179427958;179427957
N2A	25066	75421;75422;75423	chr2:178563232;178563231;178563230	chr2:179427959;179427958;179427957
N2B	18569	55930;55931;55932	chr2:178563232;178563231;178563230	chr2:179427959;179427958;179427957
Novex-1	18694	56305;56306;56307	chr2:178563232;178563231;178563230	chr2:179427959;179427958;179427957
Novex-2	18761	56506;56507;56508	chr2:178563232;178563231;178563230	chr2:179427959;179427958;179427957
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-89
• Domain position: 65
• Structural Position: 94
• Q(SASA): 0.4958
• 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
T/I	rs780363524	-0.129	0.996	N	0.559	0.372	None	gnomAD-2.1.1	1.16795E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	6.49712E-04	1.24819E-04	1.65837E-04
T/I	rs780363524	-0.129	0.996	N	0.559	0.372	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs780363524	-0.129	0.996	N	0.559	0.372	None	gnomAD-4.0.0	6.02226E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.82353E-04	0	5.98358E-05	0	1.13779E-04

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	0.0838	likely_benign	0.0874	benign	-0.534	Destabilizing	0.826	D	0.397	neutral	N	0.508286025	None	None	N
T/C	0.3505	ambiguous	0.384	ambiguous	-0.317	Destabilizing	0.999	D	0.548	neutral	None	None	None	None	N
T/D	0.3049	likely_benign	0.283	benign	0.379	Stabilizing	0.969	D	0.503	neutral	None	None	None	None	N
T/E	0.2204	likely_benign	0.1949	benign	0.318	Stabilizing	0.939	D	0.437	neutral	None	None	None	None	N
T/F	0.2665	likely_benign	0.2821	benign	-0.965	Destabilizing	0.997	D	0.615	neutral	None	None	None	None	N
T/G	0.163	likely_benign	0.167	benign	-0.686	Destabilizing	0.969	D	0.513	neutral	None	None	None	None	N
T/H	0.2305	likely_benign	0.2286	benign	-0.968	Destabilizing	0.997	D	0.609	neutral	None	None	None	None	N
T/I	0.1683	likely_benign	0.1906	benign	-0.249	Destabilizing	0.996	D	0.559	neutral	N	0.475602428	None	None	N
T/K	0.1618	likely_benign	0.1486	benign	-0.355	Destabilizing	0.079	N	0.23	neutral	None	None	None	None	N
T/L	0.0842	likely_benign	0.0929	benign	-0.249	Destabilizing	0.969	D	0.448	neutral	None	None	None	None	N
T/M	0.0861	likely_benign	0.0926	benign	-0.043	Destabilizing	0.997	D	0.551	neutral	None	None	None	None	N
T/N	0.1063	likely_benign	0.1105	benign	-0.161	Destabilizing	0.959	D	0.424	neutral	N	0.512441051	None	None	N
T/P	0.0856	likely_benign	0.0818	benign	-0.315	Destabilizing	0.996	D	0.55	neutral	N	0.514673279	None	None	N
T/Q	0.1559	likely_benign	0.1481	benign	-0.368	Destabilizing	0.982	D	0.535	neutral	None	None	None	None	N
T/R	0.1623	likely_benign	0.1471	benign	-0.117	Destabilizing	0.046	N	0.323	neutral	None	None	None	None	N
T/S	0.0954	likely_benign	0.0982	benign	-0.443	Destabilizing	0.826	D	0.405	neutral	N	0.490486911	None	None	N
T/V	0.1238	likely_benign	0.1399	benign	-0.315	Destabilizing	0.969	D	0.373	neutral	None	None	None	None	N
T/W	0.5699	likely_pathogenic	0.5578	ambiguous	-0.926	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
T/Y	0.307	likely_benign	0.3136	benign	-0.656	Destabilizing	0.997	D	0.618	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.