TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24667	74224;74225;74226	chr2:178572133;178572132;178572131	chr2:179436860;179436859;179436858
N2AB	23026	69301;69302;69303	chr2:178572133;178572132;178572131	chr2:179436860;179436859;179436858
N2A	22099	66520;66521;66522	chr2:178572133;178572132;178572131	chr2:179436860;179436859;179436858
N2B	15602	47029;47030;47031	chr2:178572133;178572132;178572131	chr2:179436860;179436859;179436858
Novex-1	15727	47404;47405;47406	chr2:178572133;178572132;178572131	chr2:179436860;179436859;179436858
Novex-2	15794	47605;47606;47607	chr2:178572133;178572132;178572131	chr2:179436860;179436859;179436858
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-67
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1411
• Predicted PPI site: N

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
A/T	None	None	0.939	N	0.538	0.155	0.283371740733	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	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
A/C	0.4207	ambiguous	0.3933	ambiguous	-0.868	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
A/D	0.7021	likely_pathogenic	0.6238	pathogenic	-1.02	Destabilizing	0.994	D	0.648	neutral	N	0.496295375	None	None	N
A/E	0.6026	likely_pathogenic	0.5214	ambiguous	-1.105	Destabilizing	0.989	D	0.597	neutral	None	None	None	None	N
A/F	0.5817	likely_pathogenic	0.4918	ambiguous	-1.062	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
A/G	0.235	likely_benign	0.2102	benign	-0.958	Destabilizing	0.697	D	0.525	neutral	N	0.497508884	None	None	N
A/H	0.6892	likely_pathogenic	0.6243	pathogenic	-1.122	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
A/I	0.3594	ambiguous	0.3015	benign	-0.432	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	N
A/K	0.7082	likely_pathogenic	0.6168	pathogenic	-1.171	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
A/L	0.261	likely_benign	0.2222	benign	-0.432	Destabilizing	0.98	D	0.525	neutral	None	None	None	None	N
A/M	0.2493	likely_benign	0.2167	benign	-0.343	Destabilizing	0.901	D	0.377	neutral	None	None	None	None	N
A/N	0.4418	ambiguous	0.3899	ambiguous	-0.834	Destabilizing	0.963	D	0.669	neutral	None	None	None	None	N
A/P	0.9595	likely_pathogenic	0.935	pathogenic	-0.504	Destabilizing	0.997	D	0.662	neutral	N	0.465506208	None	None	N
A/Q	0.5107	ambiguous	0.4501	ambiguous	-1.056	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
A/R	0.6575	likely_pathogenic	0.5836	pathogenic	-0.742	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
A/S	0.1159	likely_benign	0.1057	benign	-1.11	Destabilizing	0.045	N	0.371	neutral	N	0.487558462	None	None	N
A/T	0.0766	likely_benign	0.0744	benign	-1.108	Destabilizing	0.939	D	0.538	neutral	N	0.445018406	None	None	N
A/V	0.1695	likely_benign	0.1441	benign	-0.504	Destabilizing	0.971	D	0.529	neutral	N	0.479845843	None	None	N
A/W	0.9348	likely_pathogenic	0.8981	pathogenic	-1.327	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
A/Y	0.721	likely_pathogenic	0.6371	pathogenic	-0.956	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N

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.