TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29263	88012;88013;88014	chr2:178557475;178557474;178557473	chr2:179422202;179422201;179422200
N2AB	27622	83089;83090;83091	chr2:178557475;178557474;178557473	chr2:179422202;179422201;179422200
N2A	26695	80308;80309;80310	chr2:178557475;178557474;178557473	chr2:179422202;179422201;179422200
N2B	20198	60817;60818;60819	chr2:178557475;178557474;178557473	chr2:179422202;179422201;179422200
Novex-1	20323	61192;61193;61194	chr2:178557475;178557474;178557473	chr2:179422202;179422201;179422200
Novex-2	20390	61393;61394;61395	chr2:178557475;178557474;178557473	chr2:179422202;179422201;179422200
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-101
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4406
• 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
S/P	None	None	0.984	N	0.536	0.229	0.229264304666	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.1046	likely_benign	0.1129	benign	-0.317	Destabilizing	0.64	D	0.485	neutral	N	0.518342729	None	None	I
S/C	0.1113	likely_benign	0.1345	benign	-0.27	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	I
S/D	0.431	ambiguous	0.4541	ambiguous	0.074	Stabilizing	0.851	D	0.46	neutral	None	None	None	None	I
S/E	0.6109	likely_pathogenic	0.6246	pathogenic	-0.03	Destabilizing	0.919	D	0.472	neutral	None	None	None	None	I
S/F	0.1951	likely_benign	0.2255	benign	-0.964	Destabilizing	0.988	D	0.683	prob.neutral	None	None	None	None	I
S/G	0.1207	likely_benign	0.1368	benign	-0.405	Destabilizing	0.919	D	0.45	neutral	None	None	None	None	I
S/H	0.3495	ambiguous	0.3619	ambiguous	-0.929	Destabilizing	0.997	D	0.531	neutral	None	None	None	None	I
S/I	0.1833	likely_benign	0.1921	benign	-0.217	Destabilizing	0.976	D	0.681	prob.neutral	None	None	None	None	I
S/K	0.7507	likely_pathogenic	0.7705	pathogenic	-0.456	Destabilizing	0.919	D	0.475	neutral	None	None	None	None	I
S/L	0.1031	likely_benign	0.119	benign	-0.217	Destabilizing	0.811	D	0.595	neutral	N	0.468603172	None	None	I
S/M	0.1739	likely_benign	0.1924	benign	0.034	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	I
S/N	0.1168	likely_benign	0.1247	benign	-0.169	Destabilizing	0.132	N	0.266	neutral	None	None	None	None	I
S/P	0.8189	likely_pathogenic	0.8477	pathogenic	-0.223	Destabilizing	0.984	D	0.536	neutral	N	0.467819931	None	None	I
S/Q	0.516	ambiguous	0.5379	ambiguous	-0.441	Destabilizing	0.988	D	0.462	neutral	None	None	None	None	I
S/R	0.6973	likely_pathogenic	0.7215	pathogenic	-0.244	Destabilizing	0.988	D	0.542	neutral	None	None	None	None	I
S/T	0.0715	likely_benign	0.0766	benign	-0.276	Destabilizing	0.103	N	0.205	neutral	N	0.520324241	None	None	I
S/V	0.1821	likely_benign	0.1971	benign	-0.223	Destabilizing	0.952	D	0.602	neutral	None	None	None	None	I
S/W	0.3853	ambiguous	0.4088	ambiguous	-0.982	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
S/Y	0.2133	likely_benign	0.2218	benign	-0.695	Destabilizing	0.996	D	0.669	neutral	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.