TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6348	19267;19268;19269	chr2:178728996;178728995;178728994	chr2:179593723;179593722;179593721
N2AB	6031	18316;18317;18318	chr2:178728996;178728995;178728994	chr2:179593723;179593722;179593721
N2A	5104	15535;15536;15537	chr2:178728996;178728995;178728994	chr2:179593723;179593722;179593721
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-47
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1883
• 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/K	None	None	0.062	N	0.53	0.346	0.406668915854	gnomAD-4.0.0	1.59304E-06	None	None	None	None	I	None	0	2.29085E-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
T/A	0.0826	likely_benign	0.085	benign	-1.32	Destabilizing	None	N	0.319	neutral	N	0.498435576	None	None	I
T/C	0.3389	likely_benign	0.3552	ambiguous	-0.949	Destabilizing	0.824	D	0.566	neutral	None	None	None	None	I
T/D	0.4016	ambiguous	0.4254	ambiguous	-1.792	Destabilizing	0.38	N	0.568	neutral	None	None	None	None	I
T/E	0.2699	likely_benign	0.2854	benign	-1.563	Destabilizing	0.149	N	0.551	neutral	None	None	None	None	I
T/F	0.163	likely_benign	0.165	benign	-0.916	Destabilizing	0.555	D	0.594	neutral	None	None	None	None	I
T/G	0.2717	likely_benign	0.2825	benign	-1.735	Destabilizing	0.081	N	0.569	neutral	None	None	None	None	I
T/H	0.1827	likely_benign	0.1881	benign	-1.765	Destabilizing	0.824	D	0.605	neutral	None	None	None	None	I
T/I	0.109	likely_benign	0.1191	benign	-0.215	Destabilizing	0.002	N	0.391	neutral	D	0.53895094	None	None	I
T/K	0.1453	likely_benign	0.1581	benign	-0.518	Destabilizing	0.062	N	0.53	neutral	N	0.493965351	None	None	I
T/L	0.0838	likely_benign	0.0841	benign	-0.215	Destabilizing	0.035	N	0.489	neutral	None	None	None	None	I
T/M	0.0832	likely_benign	0.086	benign	-0.371	Destabilizing	0.555	D	0.576	neutral	None	None	None	None	I
T/N	0.1257	likely_benign	0.1287	benign	-1.278	Destabilizing	0.38	N	0.547	neutral	None	None	None	None	I
T/P	0.7023	likely_pathogenic	0.7221	pathogenic	-0.555	Destabilizing	0.317	N	0.568	neutral	D	0.542090052	None	None	I
T/Q	0.1822	likely_benign	0.1943	benign	-0.997	Destabilizing	0.38	N	0.573	neutral	None	None	None	None	I
T/R	0.1107	likely_benign	0.1218	benign	-0.79	Destabilizing	0.001	N	0.422	neutral	D	0.538641509	None	None	I
T/S	0.0965	likely_benign	0.0999	benign	-1.476	Destabilizing	0.002	N	0.468	neutral	N	0.474859389	None	None	I
T/V	0.0914	likely_benign	0.1017	benign	-0.555	Destabilizing	0.035	N	0.483	neutral	None	None	None	None	I
T/W	0.5065	ambiguous	0.5033	ambiguous	-1.118	Destabilizing	0.935	D	0.666	neutral	None	None	None	None	I
T/Y	0.1996	likely_benign	0.2086	benign	-0.717	Destabilizing	0.555	D	0.605	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.