TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29339	88240;88241;88242	chr2:178557139;178557138;178557137	chr2:179421866;179421865;179421864
N2AB	27698	83317;83318;83319	chr2:178557139;178557138;178557137	chr2:179421866;179421865;179421864
N2A	26771	80536;80537;80538	chr2:178557139;178557138;178557137	chr2:179421866;179421865;179421864
N2B	20274	61045;61046;61047	chr2:178557139;178557138;178557137	chr2:179421866;179421865;179421864
Novex-1	20399	61420;61421;61422	chr2:178557139;178557138;178557137	chr2:179421866;179421865;179421864
Novex-2	20466	61621;61622;61623	chr2:178557139;178557138;178557137	chr2:179421866;179421865;179421864
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: Fn3-102
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1077
• 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/A	rs1701796563	None	0.955	D	0.789	0.652	0.619614305854	gnomAD-4.0.0	1.36884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7991E-06	0	0
P/L	None	None	0.993	D	0.919	0.599	0.848996489152	gnomAD-4.0.0	3.42183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49766E-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
P/A	0.8862	likely_pathogenic	0.858	pathogenic	-2.301	Highly Destabilizing	0.955	D	0.789	deleterious	D	0.567311105	None	None	N
P/C	0.9921	likely_pathogenic	0.9895	pathogenic	-2.011	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
P/D	0.9991	likely_pathogenic	0.9992	pathogenic	-3.32	Highly Destabilizing	0.995	D	0.84	deleterious	None	None	None	None	N
P/E	0.9976	likely_pathogenic	0.9976	pathogenic	-3.061	Highly Destabilizing	0.995	D	0.836	deleterious	None	None	None	None	N
P/F	0.9994	likely_pathogenic	0.9992	pathogenic	-1.171	Destabilizing	1.0	D	0.942	deleterious	None	None	None	None	N
P/G	0.9938	likely_pathogenic	0.9926	pathogenic	-2.832	Highly Destabilizing	0.966	D	0.867	deleterious	None	None	None	None	N
P/H	0.9975	likely_pathogenic	0.9967	pathogenic	-2.626	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
P/I	0.9828	likely_pathogenic	0.9769	pathogenic	-0.775	Destabilizing	0.998	D	0.931	deleterious	None	None	None	None	N
P/K	0.9983	likely_pathogenic	0.9982	pathogenic	-1.805	Destabilizing	0.995	D	0.838	deleterious	None	None	None	None	N
P/L	0.952	likely_pathogenic	0.938	pathogenic	-0.775	Destabilizing	0.993	D	0.919	deleterious	D	0.567311105	None	None	N
P/M	0.9949	likely_pathogenic	0.9934	pathogenic	-1.159	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
P/N	0.9989	likely_pathogenic	0.9987	pathogenic	-2.33	Highly Destabilizing	0.995	D	0.913	deleterious	None	None	None	None	N
P/Q	0.9956	likely_pathogenic	0.9943	pathogenic	-2.07	Highly Destabilizing	0.997	D	0.863	deleterious	D	0.556715268	None	None	N
P/R	0.9946	likely_pathogenic	0.9935	pathogenic	-1.762	Destabilizing	0.993	D	0.913	deleterious	D	0.574654939	None	None	N
P/S	0.9861	likely_pathogenic	0.9821	pathogenic	-2.827	Highly Destabilizing	0.568	D	0.688	prob.neutral	D	0.574401449	None	None	N
P/T	0.9797	likely_pathogenic	0.9748	pathogenic	-2.433	Highly Destabilizing	0.987	D	0.827	deleterious	D	0.563045144	None	None	N
P/V	0.9508	likely_pathogenic	0.935	pathogenic	-1.264	Destabilizing	0.995	D	0.913	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.762	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/Y	0.9995	likely_pathogenic	0.9994	pathogenic	-1.471	Destabilizing	1.0	D	0.942	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.