TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27556	82891;82892;82893	chr2:178563466;178563465;178563464	chr2:179428193;179428192;179428191
N2AB	25915	77968;77969;77970	chr2:178563466;178563465;178563464	chr2:179428193;179428192;179428191
N2A	24988	75187;75188;75189	chr2:178563466;178563465;178563464	chr2:179428193;179428192;179428191
N2B	18491	55696;55697;55698	chr2:178563466;178563465;178563464	chr2:179428193;179428192;179428191
Novex-1	18616	56071;56072;56073	chr2:178563466;178563465;178563464	chr2:179428193;179428192;179428191
Novex-2	18683	56272;56273;56274	chr2:178563466;178563465;178563464	chr2:179428193;179428192;179428191
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-88
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1595
• 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/G	rs1181121628	-1.004	0.999	D	0.887	0.626	0.49908893446	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
S/G	rs1181121628	-1.004	0.999	D	0.887	0.626	0.49908893446	gnomAD-4.0.0	1.36851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79899E-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
S/A	0.3398	likely_benign	0.5125	ambiguous	-0.665	Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	N
S/C	0.4294	ambiguous	0.5743	pathogenic	-0.856	Destabilizing	1.0	D	0.889	deleterious	D	0.573311812	None	None	N
S/D	0.9903	likely_pathogenic	0.99	pathogenic	-1.857	Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
S/E	0.9914	likely_pathogenic	0.9926	pathogenic	-1.749	Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
S/F	0.986	likely_pathogenic	0.9918	pathogenic	-0.543	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
S/G	0.35	ambiguous	0.4283	ambiguous	-0.98	Destabilizing	0.999	D	0.887	deleterious	D	0.528340663	None	None	N
S/H	0.9871	likely_pathogenic	0.9891	pathogenic	-1.431	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
S/I	0.9632	likely_pathogenic	0.9775	pathogenic	0.095	Stabilizing	1.0	D	0.923	deleterious	D	0.572804833	None	None	N
S/K	0.9982	likely_pathogenic	0.9984	pathogenic	-0.865	Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
S/L	0.8105	likely_pathogenic	0.891	pathogenic	0.095	Stabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
S/M	0.9279	likely_pathogenic	0.9549	pathogenic	0.075	Stabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
S/N	0.9539	likely_pathogenic	0.962	pathogenic	-1.318	Destabilizing	0.999	D	0.902	deleterious	D	0.572551344	None	None	N
S/P	0.9714	likely_pathogenic	0.9811	pathogenic	-0.125	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
S/Q	0.9879	likely_pathogenic	0.9903	pathogenic	-1.289	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
S/R	0.9954	likely_pathogenic	0.9959	pathogenic	-0.936	Destabilizing	1.0	D	0.9	deleterious	D	0.55368662	None	None	N
S/T	0.4567	ambiguous	0.5	ambiguous	-0.99	Destabilizing	0.999	D	0.899	deleterious	D	0.535782948	None	None	N
S/V	0.892	likely_pathogenic	0.943	pathogenic	-0.125	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
S/W	0.989	likely_pathogenic	0.9912	pathogenic	-0.783	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
S/Y	0.9853	likely_pathogenic	0.9883	pathogenic	-0.391	Destabilizing	1.0	D	0.923	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.