TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26393	79402;79403;79404	chr2:178566955;178566954;178566953	chr2:179431682;179431681;179431680
N2AB	24752	74479;74480;74481	chr2:178566955;178566954;178566953	chr2:179431682;179431681;179431680
N2A	23825	71698;71699;71700	chr2:178566955;178566954;178566953	chr2:179431682;179431681;179431680
N2B	17328	52207;52208;52209	chr2:178566955;178566954;178566953	chr2:179431682;179431681;179431680
Novex-1	17453	52582;52583;52584	chr2:178566955;178566954;178566953	chr2:179431682;179431681;179431680
Novex-2	17520	52783;52784;52785	chr2:178566955;178566954;178566953	chr2:179431682;179431681;179431680
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-80
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2059
• 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
L/F	None	None	0.901	N	0.711	0.252	0.446310458034	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/S	rs745768515	-3.001	0.901	N	0.772	0.443	0.543076009278	gnomAD-4.0.0	2.7371E-06	None	None	None	None	N	None	5.978E-05	0	None	0	0	None	0	1.73491E-04	0	0	1.657E-05

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
L/A	0.3873	ambiguous	0.3546	ambiguous	-2.27	Highly Destabilizing	0.633	D	0.662	neutral	None	None	None	None	N
L/C	0.6554	likely_pathogenic	0.6223	pathogenic	-1.8	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	N
L/D	0.9769	likely_pathogenic	0.9793	pathogenic	-2.624	Highly Destabilizing	0.961	D	0.822	deleterious	None	None	None	None	N
L/E	0.8791	likely_pathogenic	0.8879	pathogenic	-2.497	Highly Destabilizing	0.923	D	0.816	deleterious	None	None	None	None	N
L/F	0.5373	ambiguous	0.4941	ambiguous	-1.449	Destabilizing	0.901	D	0.711	prob.delet.	N	0.484701597	None	None	N
L/G	0.8543	likely_pathogenic	0.8449	pathogenic	-2.717	Highly Destabilizing	0.923	D	0.798	deleterious	None	None	None	None	N
L/H	0.8549	likely_pathogenic	0.8607	pathogenic	-2.145	Highly Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
L/I	0.1009	likely_benign	0.0814	benign	-1.024	Destabilizing	0.372	N	0.691	prob.neutral	None	None	None	None	N
L/K	0.8775	likely_pathogenic	0.9003	pathogenic	-1.662	Destabilizing	0.923	D	0.785	deleterious	None	None	None	None	N
L/M	0.1944	likely_benign	0.1724	benign	-1.075	Destabilizing	0.901	D	0.672	neutral	N	0.515176116	None	None	N
L/N	0.8832	likely_pathogenic	0.874	pathogenic	-1.794	Destabilizing	0.961	D	0.827	deleterious	None	None	None	None	N
L/P	0.2018	likely_benign	0.2488	benign	-1.416	Destabilizing	0.011	N	0.499	neutral	None	None	None	None	N
L/Q	0.688	likely_pathogenic	0.7027	pathogenic	-1.825	Destabilizing	0.961	D	0.796	deleterious	None	None	None	None	N
L/R	0.8129	likely_pathogenic	0.8456	pathogenic	-1.269	Destabilizing	0.961	D	0.801	deleterious	None	None	None	None	N
L/S	0.7436	likely_pathogenic	0.7084	pathogenic	-2.423	Highly Destabilizing	0.901	D	0.772	deleterious	N	0.515683095	None	None	N
L/T	0.3696	ambiguous	0.3333	benign	-2.169	Highly Destabilizing	0.775	D	0.767	deleterious	None	None	None	None	N
L/V	0.0768	likely_benign	0.0678	benign	-1.416	Destabilizing	0.008	N	0.475	neutral	N	0.449125865	None	None	N
L/W	0.8295	likely_pathogenic	0.8402	pathogenic	-1.745	Destabilizing	0.995	D	0.786	deleterious	D	0.527546379	None	None	N
L/Y	0.8927	likely_pathogenic	0.8911	pathogenic	-1.472	Destabilizing	0.961	D	0.74	deleterious	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.