TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1789	5590;5591;5592	chr2:178776499;178776498;178776497	chr2:179641226;179641225;179641224
N2AB	1789	5590;5591;5592	chr2:178776499;178776498;178776497	chr2:179641226;179641225;179641224
N2A	1789	5590;5591;5592	chr2:178776499;178776498;178776497	chr2:179641226;179641225;179641224
N2B	1743	5452;5453;5454	chr2:178776499;178776498;178776497	chr2:179641226;179641225;179641224
Novex-1	1743	5452;5453;5454	chr2:178776499;178776498;178776497	chr2:179641226;179641225;179641224
Novex-2	1743	5452;5453;5454	chr2:178776499;178776498;178776497	chr2:179641226;179641225;179641224
Novex-3	1789	5590;5591;5592	chr2:178776499;178776498;178776497	chr2:179641226;179641225;179641224

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-8
• Domain position: 87
• Structural Position: 171
• Q(SASA): 0.4059
• 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
S/F	rs2092243043	None	1.0	D	0.911	0.609	0.754366180968	gnomAD-4.0.0	3.21046E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7135E-06	0	0
S/P	rs775865795	-0.319	1.0	D	0.879	0.656	0.554681544945	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	5.52E-05	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
S/A	0.1756	likely_benign	0.1904	benign	-0.635	Destabilizing	0.997	D	0.558	neutral	D	0.539379265	None	None	N
S/C	0.5673	likely_pathogenic	0.5956	pathogenic	-0.375	Destabilizing	1.0	D	0.861	deleterious	D	0.769055346	None	None	N
S/D	0.945	likely_pathogenic	0.9526	pathogenic	-0.252	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
S/E	0.9146	likely_pathogenic	0.9317	pathogenic	-0.278	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
S/F	0.7946	likely_pathogenic	0.8274	pathogenic	-0.854	Destabilizing	1.0	D	0.911	deleterious	D	0.682533259	None	None	N
S/G	0.4163	ambiguous	0.4425	ambiguous	-0.865	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
S/H	0.8205	likely_pathogenic	0.8444	pathogenic	-1.415	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/I	0.7159	likely_pathogenic	0.7745	pathogenic	-0.134	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
S/K	0.9698	likely_pathogenic	0.9786	pathogenic	-0.75	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
S/L	0.529	ambiguous	0.5766	pathogenic	-0.134	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
S/M	0.5645	likely_pathogenic	0.6063	pathogenic	0.216	Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
S/N	0.614	likely_pathogenic	0.6934	pathogenic	-0.602	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
S/P	0.9834	likely_pathogenic	0.9845	pathogenic	-0.268	Destabilizing	1.0	D	0.879	deleterious	D	0.671625738	None	None	N
S/Q	0.8268	likely_pathogenic	0.8591	pathogenic	-0.795	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
S/R	0.958	likely_pathogenic	0.9685	pathogenic	-0.626	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
S/T	0.1626	likely_benign	0.1864	benign	-0.631	Destabilizing	0.999	D	0.607	neutral	N	0.508849021	None	None	N
S/V	0.5749	likely_pathogenic	0.6418	pathogenic	-0.268	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
S/W	0.9263	likely_pathogenic	0.9268	pathogenic	-0.837	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
S/Y	0.7662	likely_pathogenic	0.7943	pathogenic	-0.585	Destabilizing	1.0	D	0.911	deleterious	D	0.694984956	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.