TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26957	81094;81095;81096	chr2:178565263;178565262;178565261	chr2:179429990;179429989;179429988
N2AB	25316	76171;76172;76173	chr2:178565263;178565262;178565261	chr2:179429990;179429989;179429988
N2A	24389	73390;73391;73392	chr2:178565263;178565262;178565261	chr2:179429990;179429989;179429988
N2B	17892	53899;53900;53901	chr2:178565263;178565262;178565261	chr2:179429990;179429989;179429988
Novex-1	18017	54274;54275;54276	chr2:178565263;178565262;178565261	chr2:179429990;179429989;179429988
Novex-2	18084	54475;54476;54477	chr2:178565263;178565262;178565261	chr2:179429990;179429989;179429988
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-139
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.364
• 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
S/N	None	None	0.003	N	0.159	0.086	0.0954503805726	gnomAD-4.0.0	1.59154E-06	None	None	None	None	I	None	0	2.28676E-05	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
S/A	0.0675	likely_benign	0.0683	benign	-0.19	Destabilizing	0.004	N	0.169	neutral	None	None	None	None	I
S/C	0.1321	likely_benign	0.1279	benign	-0.463	Destabilizing	0.983	D	0.324	neutral	N	0.521085735	None	None	I
S/D	0.3452	ambiguous	0.3534	ambiguous	-0.15	Destabilizing	0.59	D	0.231	neutral	None	None	None	None	I
S/E	0.4075	ambiguous	0.4333	ambiguous	-0.262	Destabilizing	0.742	D	0.239	neutral	None	None	None	None	I
S/F	0.1739	likely_benign	0.1725	benign	-0.954	Destabilizing	0.953	D	0.453	neutral	None	None	None	None	I
S/G	0.0862	likely_benign	0.0851	benign	-0.213	Destabilizing	0.309	N	0.293	neutral	D	0.537929433	None	None	I
S/H	0.2895	likely_benign	0.2998	benign	-0.529	Destabilizing	0.953	D	0.327	neutral	None	None	None	None	I
S/I	0.1006	likely_benign	0.0974	benign	-0.258	Destabilizing	0.884	D	0.449	neutral	N	0.518516953	None	None	I
S/K	0.4355	ambiguous	0.461	ambiguous	-0.466	Destabilizing	0.742	D	0.247	neutral	None	None	None	None	I
S/L	0.0764	likely_benign	0.0725	benign	-0.258	Destabilizing	0.59	D	0.389	neutral	None	None	None	None	I
S/M	0.1401	likely_benign	0.1385	benign	-0.214	Destabilizing	0.984	D	0.326	neutral	None	None	None	None	I
S/N	0.1093	likely_benign	0.1089	benign	-0.259	Destabilizing	0.003	N	0.159	neutral	N	0.487470891	None	None	I
S/P	0.1819	likely_benign	0.1785	benign	-0.213	Destabilizing	0.953	D	0.338	neutral	None	None	None	None	I
S/Q	0.3746	ambiguous	0.3916	ambiguous	-0.483	Destabilizing	0.91	D	0.287	neutral	None	None	None	None	I
S/R	0.3897	ambiguous	0.4045	ambiguous	-0.214	Destabilizing	0.684	D	0.359	neutral	N	0.490825026	None	None	I
S/T	0.0637	likely_benign	0.0641	benign	-0.364	Destabilizing	0.012	N	0.152	neutral	N	0.51082019	None	None	I
S/V	0.1137	likely_benign	0.1107	benign	-0.213	Destabilizing	0.59	D	0.403	neutral	None	None	None	None	I
S/W	0.3688	ambiguous	0.3688	ambiguous	-1.048	Destabilizing	0.996	D	0.515	neutral	None	None	None	None	I
S/Y	0.1976	likely_benign	0.1964	benign	-0.736	Destabilizing	0.984	D	0.452	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.