TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29618	89077;89078;89079	chr2:178554495;178554494;178554493	chr2:179419222;179419221;179419220
N2AB	27977	84154;84155;84156	chr2:178554495;178554494;178554493	chr2:179419222;179419221;179419220
N2A	27050	81373;81374;81375	chr2:178554495;178554494;178554493	chr2:179419222;179419221;179419220
N2B	20553	61882;61883;61884	chr2:178554495;178554494;178554493	chr2:179419222;179419221;179419220
Novex-1	20678	62257;62258;62259	chr2:178554495;178554494;178554493	chr2:179419222;179419221;179419220
Novex-2	20745	62458;62459;62460	chr2:178554495;178554494;178554493	chr2:179419222;179419221;179419220
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-103
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.3892
• 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
E/K	rs879222602	-0.058	0.426	N	0.493	0.23	None	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.99E-06	0
E/K	rs879222602	-0.058	0.426	N	0.493	0.23	None	gnomAD-4.0.0	1.98497E-05	None	None	None	None	N	None	2.98757E-05	0	None	0	2.52985E-05	None	0	0	2.33889E-05	0	1.65793E-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
E/A	0.1122	likely_benign	0.1214	benign	-0.767	Destabilizing	0.002	N	0.247	neutral	N	0.518692232	None	None	N
E/C	0.6429	likely_pathogenic	0.6717	pathogenic	-0.391	Destabilizing	0.935	D	0.597	neutral	None	None	None	None	N
E/D	0.0615	likely_benign	0.0639	benign	-0.839	Destabilizing	None	N	0.073	neutral	N	0.456625053	None	None	N
E/F	0.5271	ambiguous	0.5655	pathogenic	-0.436	Destabilizing	0.791	D	0.579	neutral	None	None	None	None	N
E/G	0.1546	likely_benign	0.1637	benign	-1.054	Destabilizing	0.117	N	0.491	neutral	N	0.488801476	None	None	N
E/H	0.3262	likely_benign	0.3572	ambiguous	-0.545	Destabilizing	0.555	D	0.492	neutral	None	None	None	None	N
E/I	0.1961	likely_benign	0.2079	benign	-0.01	Destabilizing	0.555	D	0.562	neutral	None	None	None	None	N
E/K	0.1235	likely_benign	0.1316	benign	-0.413	Destabilizing	0.426	N	0.493	neutral	N	0.504320213	None	None	N
E/L	0.2237	likely_benign	0.2398	benign	-0.01	Destabilizing	0.149	N	0.572	neutral	None	None	None	None	N
E/M	0.3069	likely_benign	0.3267	benign	0.271	Stabilizing	0.935	D	0.563	neutral	None	None	None	None	N
E/N	0.1275	likely_benign	0.1424	benign	-0.732	Destabilizing	0.081	N	0.523	neutral	None	None	None	None	N
E/P	0.2474	likely_benign	0.2493	benign	-0.242	Destabilizing	0.555	D	0.575	neutral	None	None	None	None	N
E/Q	0.121	likely_benign	0.127	benign	-0.669	Destabilizing	0.251	N	0.558	neutral	N	0.497586242	None	None	N
E/R	0.2154	likely_benign	0.2264	benign	-0.127	Destabilizing	0.38	N	0.523	neutral	None	None	None	None	N
E/S	0.1341	likely_benign	0.1462	benign	-0.973	Destabilizing	0.081	N	0.415	neutral	None	None	None	None	N
E/T	0.1706	likely_benign	0.181	benign	-0.749	Destabilizing	0.149	N	0.544	neutral	None	None	None	None	N
E/V	0.1287	likely_benign	0.1363	benign	-0.242	Destabilizing	0.117	N	0.576	neutral	N	0.518654947	None	None	N
E/W	0.7935	likely_pathogenic	0.8144	pathogenic	-0.22	Destabilizing	0.935	D	0.679	prob.neutral	None	None	None	None	N
E/Y	0.3714	ambiguous	0.4016	ambiguous	-0.203	Destabilizing	0.791	D	0.579	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.