TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25699	77320;77321;77322	chr2:178569037;178569036;178569035	chr2:179433764;179433763;179433762
N2AB	24058	72397;72398;72399	chr2:178569037;178569036;178569035	chr2:179433764;179433763;179433762
N2A	23131	69616;69617;69618	chr2:178569037;178569036;178569035	chr2:179433764;179433763;179433762
N2B	16634	50125;50126;50127	chr2:178569037;178569036;178569035	chr2:179433764;179433763;179433762
Novex-1	16759	50500;50501;50502	chr2:178569037;178569036;178569035	chr2:179433764;179433763;179433762
Novex-2	16826	50701;50702;50703	chr2:178569037;178569036;178569035	chr2:179433764;179433763;179433762
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-75
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1067
• 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
P/S	rs1435124022	None	1.0	D	0.752	0.609	0.491248951702	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1435124022	None	1.0	D	0.752	0.609	0.491248951702	gnomAD-4.0.0	6.57756E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47093E-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
P/A	0.937	likely_pathogenic	0.9426	pathogenic	-1.966	Destabilizing	1.0	D	0.801	deleterious	D	0.533694763	None	None	N
P/C	0.9944	likely_pathogenic	0.9946	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.422	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
P/E	0.9992	likely_pathogenic	0.999	pathogenic	-3.315	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9996	pathogenic	-1.211	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
P/G	0.9968	likely_pathogenic	0.9968	pathogenic	-2.337	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/H	0.9987	likely_pathogenic	0.9986	pathogenic	-1.744	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
P/I	0.992	likely_pathogenic	0.9899	pathogenic	-0.967	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.9992	pathogenic	-1.755	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
P/L	0.9574	likely_pathogenic	0.9535	pathogenic	-0.967	Destabilizing	1.0	D	0.819	deleterious	D	0.555304511	None	None	N
P/M	0.9965	likely_pathogenic	0.9962	pathogenic	-1.214	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/N	0.9995	likely_pathogenic	0.9995	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/Q	0.9978	likely_pathogenic	0.9978	pathogenic	-2.145	Highly Destabilizing	1.0	D	0.829	deleterious	D	0.557332427	None	None	N
P/R	0.997	likely_pathogenic	0.9968	pathogenic	-1.319	Destabilizing	1.0	D	0.813	deleterious	D	0.545558048	None	None	N
P/S	0.9931	likely_pathogenic	0.9931	pathogenic	-2.47	Highly Destabilizing	1.0	D	0.752	deleterious	D	0.545304558	None	None	N
P/T	0.9901	likely_pathogenic	0.9891	pathogenic	-2.259	Highly Destabilizing	1.0	D	0.76	deleterious	D	0.556571958	None	None	N
P/V	0.9813	likely_pathogenic	0.977	pathogenic	-1.275	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.588	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9997	pathogenic	-1.317	Destabilizing	1.0	D	0.849	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.