TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21934	66025;66026;66027	chr2:178583003;178583002;178583001	chr2:179447730;179447729;179447728
N2AB	20293	61102;61103;61104	chr2:178583003;178583002;178583001	chr2:179447730;179447729;179447728
N2A	19366	58321;58322;58323	chr2:178583003;178583002;178583001	chr2:179447730;179447729;179447728
N2B	12869	38830;38831;38832	chr2:178583003;178583002;178583001	chr2:179447730;179447729;179447728
Novex-1	12994	39205;39206;39207	chr2:178583003;178583002;178583001	chr2:179447730;179447729;179447728
Novex-2	13061	39406;39407;39408	chr2:178583003;178583002;178583001	chr2:179447730;179447729;179447728
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-125
• Domain position: 69
• Structural Position: 154
• Q(SASA): 0.1083
• 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
Y/C	None	None	0.999	D	0.825	0.799	0.801429400344	gnomAD-4.0.0	7.20203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87513E-06	0	0
Y/D	rs786205385	None	0.967	D	0.867	0.797	0.901314349755	gnomAD-4.0.0	3.28938E-06	None	None	None	None	N	None	0	2.37338E-05	None	0	0	None	0	0	0	0	3.10617E-05
Y/H	None	None	0.994	D	0.699	0.806	0.750646069438	gnomAD-4.0.0	3.28938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.9102E-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
Y/A	0.9977	likely_pathogenic	0.9974	pathogenic	-2.332	Highly Destabilizing	0.845	D	0.811	deleterious	None	None	None	None	N
Y/C	0.9372	likely_pathogenic	0.9321	pathogenic	-1.801	Destabilizing	0.999	D	0.825	deleterious	D	0.635314553	None	None	N
Y/D	0.9986	likely_pathogenic	0.9982	pathogenic	-3.079	Highly Destabilizing	0.967	D	0.867	deleterious	D	0.635314553	None	None	N
Y/E	0.9995	likely_pathogenic	0.9995	pathogenic	-2.832	Highly Destabilizing	0.975	D	0.82	deleterious	None	None	None	None	N
Y/F	0.1739	likely_benign	0.163	benign	-0.777	Destabilizing	0.944	D	0.677	prob.neutral	D	0.560195005	None	None	N
Y/G	0.996	likely_pathogenic	0.9955	pathogenic	-2.792	Highly Destabilizing	0.845	D	0.834	deleterious	None	None	None	None	N
Y/H	0.9765	likely_pathogenic	0.9751	pathogenic	-2.122	Highly Destabilizing	0.994	D	0.699	prob.neutral	D	0.618861223	None	None	N
Y/I	0.9408	likely_pathogenic	0.9396	pathogenic	-0.808	Destabilizing	0.987	D	0.769	deleterious	None	None	None	None	N
Y/K	0.9989	likely_pathogenic	0.9987	pathogenic	-1.891	Destabilizing	0.975	D	0.822	deleterious	None	None	None	None	N
Y/L	0.9057	likely_pathogenic	0.9055	pathogenic	-0.808	Destabilizing	0.916	D	0.749	deleterious	None	None	None	None	N
Y/M	0.9804	likely_pathogenic	0.98	pathogenic	-0.965	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
Y/N	0.9912	likely_pathogenic	0.9908	pathogenic	-2.818	Highly Destabilizing	0.967	D	0.843	deleterious	D	0.619063027	None	None	N
Y/P	0.9996	likely_pathogenic	0.9994	pathogenic	-1.332	Destabilizing	0.987	D	0.87	deleterious	None	None	None	None	N
Y/Q	0.999	likely_pathogenic	0.999	pathogenic	-2.388	Highly Destabilizing	0.975	D	0.773	deleterious	None	None	None	None	N
Y/R	0.9954	likely_pathogenic	0.9952	pathogenic	-2.119	Highly Destabilizing	0.975	D	0.856	deleterious	None	None	None	None	N
Y/S	0.9941	likely_pathogenic	0.9935	pathogenic	-3.135	Highly Destabilizing	0.204	N	0.695	prob.neutral	D	0.635314553	None	None	N
Y/T	0.997	likely_pathogenic	0.9966	pathogenic	-2.737	Highly Destabilizing	0.95	D	0.814	deleterious	None	None	None	None	N
Y/V	0.9244	likely_pathogenic	0.9193	pathogenic	-1.332	Destabilizing	0.975	D	0.755	deleterious	None	None	None	None	N
Y/W	0.8326	likely_pathogenic	0.8047	pathogenic	-0.168	Destabilizing	0.999	D	0.688	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.