TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6865	20818;20819;20820	chr2:178725611;178725610;178725609	chr2:179590338;179590337;179590336
N2AB	6548	19867;19868;19869	chr2:178725611;178725610;178725609	chr2:179590338;179590337;179590336
N2A	5621	17086;17087;17088	chr2:178725611;178725610;178725609	chr2:179590338;179590337;179590336
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-53
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.6064
• 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
V/F	None	None	0.901	N	0.422	0.522	0.774875236417	gnomAD-4.0.0	6.88996E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.18655E-05	0
V/I	rs2154304381	None	0.008	D	0.171	0.152	0.328752806141	gnomAD-4.0.0	6.88996E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.03566E-07	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
V/A	0.1309	likely_benign	0.1316	benign	-1.647	Destabilizing	0.014	N	0.142	neutral	N	0.489887557	None	None	I
V/C	0.722	likely_pathogenic	0.731	pathogenic	-1.138	Destabilizing	0.996	D	0.439	neutral	None	None	None	None	I
V/D	0.6611	likely_pathogenic	0.7161	pathogenic	-1.478	Destabilizing	0.949	D	0.492	neutral	D	0.529838828	None	None	I
V/E	0.544	ambiguous	0.5871	pathogenic	-1.422	Destabilizing	0.961	D	0.423	neutral	None	None	None	None	I
V/F	0.2152	likely_benign	0.2428	benign	-1.125	Destabilizing	0.901	D	0.422	neutral	N	0.510974105	None	None	I
V/G	0.3038	likely_benign	0.3251	benign	-2.022	Highly Destabilizing	0.565	D	0.45	neutral	N	0.506454654	None	None	I
V/H	0.7284	likely_pathogenic	0.7454	pathogenic	-1.554	Destabilizing	0.996	D	0.512	neutral	None	None	None	None	I
V/I	0.0878	likely_benign	0.0846	benign	-0.687	Destabilizing	0.008	N	0.171	neutral	D	0.525963	None	None	I
V/K	0.5213	ambiguous	0.5588	ambiguous	-1.273	Destabilizing	0.923	D	0.427	neutral	None	None	None	None	I
V/L	0.2343	likely_benign	0.2271	benign	-0.687	Destabilizing	0.156	N	0.413	neutral	N	0.515187159	None	None	I
V/M	0.1655	likely_benign	0.1581	benign	-0.616	Destabilizing	0.923	D	0.466	neutral	None	None	None	None	I
V/N	0.5074	ambiguous	0.5274	ambiguous	-1.168	Destabilizing	0.987	D	0.509	neutral	None	None	None	None	I
V/P	0.8367	likely_pathogenic	0.8736	pathogenic	-0.974	Destabilizing	0.961	D	0.456	neutral	None	None	None	None	I
V/Q	0.5257	ambiguous	0.5547	ambiguous	-1.267	Destabilizing	0.987	D	0.48	neutral	None	None	None	None	I
V/R	0.4249	ambiguous	0.4715	ambiguous	-0.86	Destabilizing	0.961	D	0.51	neutral	None	None	None	None	I
V/S	0.2767	likely_benign	0.277	benign	-1.767	Destabilizing	0.633	D	0.411	neutral	None	None	None	None	I
V/T	0.1664	likely_benign	0.1517	benign	-1.597	Destabilizing	0.775	D	0.39	neutral	None	None	None	None	I
V/W	0.8767	likely_pathogenic	0.8924	pathogenic	-1.377	Destabilizing	0.996	D	0.601	neutral	None	None	None	None	I
V/Y	0.6643	likely_pathogenic	0.7007	pathogenic	-1.059	Destabilizing	0.961	D	0.425	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.