TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23857	71794;71795;71796	chr2:178574563;178574562;178574561	chr2:179439290;179439289;179439288
N2AB	22216	66871;66872;66873	chr2:178574563;178574562;178574561	chr2:179439290;179439289;179439288
N2A	21289	64090;64091;64092	chr2:178574563;178574562;178574561	chr2:179439290;179439289;179439288
N2B	14792	44599;44600;44601	chr2:178574563;178574562;178574561	chr2:179439290;179439289;179439288
Novex-1	14917	44974;44975;44976	chr2:178574563;178574562;178574561	chr2:179439290;179439289;179439288
Novex-2	14984	45175;45176;45177	chr2:178574563;178574562;178574561	chr2:179439290;179439289;179439288
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-61
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6381
• 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
P/L	None	None	0.454	N	0.445	0.327	0.498065138572	gnomAD-4.0.0	1.59173E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8593E-06	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
P/A	0.0689	likely_benign	0.0687	benign	-0.603	Destabilizing	0.625	D	0.367	neutral	N	0.514942638	None	None	I
P/C	0.3539	ambiguous	0.3424	ambiguous	-0.565	Destabilizing	0.998	D	0.463	neutral	None	None	None	None	I
P/D	0.3459	ambiguous	0.3302	benign	-0.387	Destabilizing	0.842	D	0.429	neutral	None	None	None	None	I
P/E	0.1961	likely_benign	0.1937	benign	-0.494	Destabilizing	0.728	D	0.36	neutral	None	None	None	None	I
P/F	0.434	ambiguous	0.4072	ambiguous	-0.776	Destabilizing	0.974	D	0.499	neutral	None	None	None	None	I
P/G	0.2773	likely_benign	0.2627	benign	-0.766	Destabilizing	0.842	D	0.466	neutral	None	None	None	None	I
P/H	0.1434	likely_benign	0.1406	benign	-0.33	Destabilizing	0.997	D	0.453	neutral	N	0.506531019	None	None	I
P/I	0.2184	likely_benign	0.2022	benign	-0.318	Destabilizing	0.067	N	0.368	neutral	None	None	None	None	I
P/K	0.1601	likely_benign	0.1598	benign	-0.492	Destabilizing	0.007	N	0.123	neutral	None	None	None	None	I
P/L	0.1022	likely_benign	0.0986	benign	-0.318	Destabilizing	0.454	N	0.445	neutral	N	0.511406091	None	None	I
P/M	0.2279	likely_benign	0.2118	benign	-0.27	Destabilizing	0.974	D	0.465	neutral	None	None	None	None	I
P/N	0.2316	likely_benign	0.219	benign	-0.177	Destabilizing	0.949	D	0.479	neutral	None	None	None	None	I
P/Q	0.1065	likely_benign	0.1017	benign	-0.438	Destabilizing	0.949	D	0.449	neutral	None	None	None	None	I
P/R	0.1193	likely_benign	0.1184	benign	0.056	Stabilizing	0.876	D	0.447	neutral	N	0.477564211	None	None	I
P/S	0.1094	likely_benign	0.1096	benign	-0.567	Destabilizing	0.801	D	0.36	neutral	N	0.478930109	None	None	I
P/T	0.0899	likely_benign	0.0882	benign	-0.571	Destabilizing	0.801	D	0.366	neutral	N	0.49712327	None	None	I
P/V	0.1375	likely_benign	0.1323	benign	-0.377	Destabilizing	0.067	N	0.223	neutral	None	None	None	None	I
P/W	0.6238	likely_pathogenic	0.5761	pathogenic	-0.855	Destabilizing	0.998	D	0.574	neutral	None	None	None	None	I
P/Y	0.3828	ambiguous	0.3516	ambiguous	-0.555	Destabilizing	0.991	D	0.496	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.