TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29240	87943;87944;87945	chr2:178557544;178557543;178557542	chr2:179422271;179422270;179422269
N2AB	27599	83020;83021;83022	chr2:178557544;178557543;178557542	chr2:179422271;179422270;179422269
N2A	26672	80239;80240;80241	chr2:178557544;178557543;178557542	chr2:179422271;179422270;179422269
N2B	20175	60748;60749;60750	chr2:178557544;178557543;178557542	chr2:179422271;179422270;179422269
Novex-1	20300	61123;61124;61125	chr2:178557544;178557543;178557542	chr2:179422271;179422270;179422269
Novex-2	20367	61324;61325;61326	chr2:178557544;178557543;178557542	chr2:179422271;179422270;179422269
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: Fn3-101
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2964
• Predicted PPI site: I

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	None	None	0.956	N	0.706	0.349	0.316198179892	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
P/T	None	None	0.978	N	0.736	0.384	0.502878934189	gnomAD-4.0.0	3.60098E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93752E-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	0.1316	likely_benign	0.1267	benign	-1.36	Destabilizing	0.198	N	0.377	neutral	N	0.475013239	None	None	I
P/C	0.7002	likely_pathogenic	0.7283	pathogenic	-1.111	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
P/D	0.9463	likely_pathogenic	0.9455	pathogenic	-1.311	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	I
P/E	0.7395	likely_pathogenic	0.7007	pathogenic	-1.358	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	I
P/F	0.788	likely_pathogenic	0.8	pathogenic	-1.318	Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	I
P/G	0.7395	likely_pathogenic	0.7448	pathogenic	-1.605	Destabilizing	0.967	D	0.761	deleterious	None	None	None	None	I
P/H	0.57	likely_pathogenic	0.5746	pathogenic	-1.088	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/I	0.5747	likely_pathogenic	0.5712	pathogenic	-0.803	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	I
P/K	0.7461	likely_pathogenic	0.7347	pathogenic	-0.944	Destabilizing	0.995	D	0.749	deleterious	None	None	None	None	I
P/L	0.3348	likely_benign	0.3879	ambiguous	-0.803	Destabilizing	0.978	D	0.809	deleterious	D	0.522331096	None	None	I
P/M	0.5467	ambiguous	0.552	ambiguous	-0.653	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
P/N	0.7942	likely_pathogenic	0.782	pathogenic	-0.739	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	I
P/Q	0.4049	ambiguous	0.3998	ambiguous	-1.027	Destabilizing	0.999	D	0.725	prob.delet.	N	0.486323169	None	None	I
P/R	0.5936	likely_pathogenic	0.6011	pathogenic	-0.408	Destabilizing	0.997	D	0.799	deleterious	N	0.509542759	None	None	I
P/S	0.318	likely_benign	0.3217	benign	-1.228	Destabilizing	0.956	D	0.706	prob.neutral	N	0.486069679	None	None	I
P/T	0.3623	ambiguous	0.3492	ambiguous	-1.174	Destabilizing	0.978	D	0.736	prob.delet.	N	0.498946922	None	None	I
P/V	0.4502	ambiguous	0.4639	ambiguous	-0.955	Destabilizing	0.983	D	0.777	deleterious	None	None	None	None	I
P/W	0.929	likely_pathogenic	0.9414	pathogenic	-1.39	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
P/Y	0.8142	likely_pathogenic	0.819	pathogenic	-1.089	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I

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.