TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32709	98350;98351;98352	chr2:178539940;178539939;178539938	chr2:179404667;179404666;179404665
N2AB	31068	93427;93428;93429	chr2:178539940;178539939;178539938	chr2:179404667;179404666;179404665
N2A	30141	90646;90647;90648	chr2:178539940;178539939;178539938	chr2:179404667;179404666;179404665
N2B	23644	71155;71156;71157	chr2:178539940;178539939;178539938	chr2:179404667;179404666;179404665
Novex-1	23769	71530;71531;71532	chr2:178539940;178539939;178539938	chr2:179404667;179404666;179404665
Novex-2	23836	71731;71732;71733	chr2:178539940;178539939;178539938	chr2:179404667;179404666;179404665
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-155
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.6228
• 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
R/G	rs1372889503	-0.121	0.175	N	0.367	0.176	0.379193981924	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	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
R/A	0.2421	likely_benign	0.304	benign	-0.055	Destabilizing	0.055	N	0.394	neutral	None	None	None	None	I
R/C	0.1978	likely_benign	0.2323	benign	-0.457	Destabilizing	0.958	D	0.293	neutral	None	None	None	None	I
R/D	0.4163	ambiguous	0.4734	ambiguous	-0.386	Destabilizing	0.22	N	0.393	neutral	None	None	None	None	I
R/E	0.2481	likely_benign	0.2789	benign	-0.3	Destabilizing	0.055	N	0.376	neutral	None	None	None	None	I
R/F	0.472	ambiguous	0.5223	ambiguous	-0.313	Destabilizing	0.667	D	0.321	neutral	None	None	None	None	I
R/G	0.1744	likely_benign	0.2137	benign	-0.241	Destabilizing	0.175	N	0.367	neutral	N	0.499498757	None	None	I
R/H	0.1183	likely_benign	0.1269	benign	-0.909	Destabilizing	0.667	D	0.336	neutral	None	None	None	None	I
R/I	0.173	likely_benign	0.2108	benign	0.402	Stabilizing	0.003	N	0.323	neutral	N	0.499672115	None	None	I
R/K	0.0858	likely_benign	0.0969	benign	-0.231	Destabilizing	None	N	0.196	neutral	N	0.422806055	None	None	I
R/L	0.1853	likely_benign	0.2185	benign	0.402	Stabilizing	0.055	N	0.333	neutral	None	None	None	None	I
R/M	0.1923	likely_benign	0.2386	benign	-0.216	Destabilizing	0.667	D	0.335	neutral	None	None	None	None	I
R/N	0.314	likely_benign	0.3815	ambiguous	-0.324	Destabilizing	0.22	N	0.344	neutral	None	None	None	None	I
R/P	0.4037	ambiguous	0.4691	ambiguous	0.269	Stabilizing	0.667	D	0.369	neutral	None	None	None	None	I
R/Q	0.1058	likely_benign	0.1154	benign	-0.271	Destabilizing	0.011	N	0.261	neutral	None	None	None	None	I
R/S	0.2829	likely_benign	0.3441	ambiguous	-0.514	Destabilizing	0.096	N	0.371	neutral	N	0.479352771	None	None	I
R/T	0.1462	likely_benign	0.1876	benign	-0.288	Destabilizing	0.175	N	0.386	neutral	N	0.455438549	None	None	I
R/V	0.2446	likely_benign	0.2913	benign	0.269	Stabilizing	0.055	N	0.318	neutral	None	None	None	None	I
R/W	0.2209	likely_benign	0.2501	benign	-0.482	Destabilizing	0.958	D	0.302	neutral	None	None	None	None	I
R/Y	0.3556	ambiguous	0.3811	ambiguous	-0.064	Destabilizing	0.859	D	0.352	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.