TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32841	98746;98747;98748	chr2:178539544;178539543;178539542	chr2:179404271;179404270;179404269
N2AB	31200	93823;93824;93825	chr2:178539544;178539543;178539542	chr2:179404271;179404270;179404269
N2A	30273	91042;91043;91044	chr2:178539544;178539543;178539542	chr2:179404271;179404270;179404269
N2B	23776	71551;71552;71553	chr2:178539544;178539543;178539542	chr2:179404271;179404270;179404269
Novex-1	23901	71926;71927;71928	chr2:178539544;178539543;178539542	chr2:179404271;179404270;179404269
Novex-2	23968	72127;72128;72129	chr2:178539544;178539543;178539542	chr2:179404271;179404270;179404269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-127
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.6629
• 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
A/T	None	None	None	N	0.181	0.043	0.167679373172	gnomAD-4.0.0	6.84185E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99462E-07	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
A/C	0.5855	likely_pathogenic	0.5168	ambiguous	-0.768	Destabilizing	0.824	D	0.318	neutral	None	None	None	None	N
A/D	0.4129	ambiguous	0.312	benign	-0.465	Destabilizing	0.062	N	0.355	neutral	N	0.380433784	None	None	N
A/E	0.3194	likely_benign	0.2578	benign	-0.588	Destabilizing	0.081	N	0.285	neutral	None	None	None	None	N
A/F	0.4703	ambiguous	0.3974	ambiguous	-0.787	Destabilizing	0.555	D	0.421	neutral	None	None	None	None	N
A/G	0.1692	likely_benign	0.142	benign	-0.364	Destabilizing	0.027	N	0.321	neutral	N	0.369693928	None	None	N
A/H	0.5407	ambiguous	0.474	ambiguous	-0.269	Destabilizing	0.824	D	0.431	neutral	None	None	None	None	N
A/I	0.3184	likely_benign	0.2465	benign	-0.277	Destabilizing	0.235	N	0.329	neutral	None	None	None	None	N
A/K	0.4562	ambiguous	0.4061	ambiguous	-0.659	Destabilizing	0.081	N	0.309	neutral	None	None	None	None	N
A/L	0.2098	likely_benign	0.1716	benign	-0.277	Destabilizing	0.081	N	0.272	neutral	None	None	None	None	N
A/M	0.2345	likely_benign	0.1926	benign	-0.53	Destabilizing	0.824	D	0.344	neutral	None	None	None	None	N
A/N	0.2429	likely_benign	0.1949	benign	-0.345	Destabilizing	0.002	N	0.291	neutral	None	None	None	None	N
A/P	0.2587	likely_benign	0.2039	benign	-0.249	Destabilizing	0.317	N	0.332	neutral	N	0.475632102	None	None	N
A/Q	0.34	ambiguous	0.3074	benign	-0.574	Destabilizing	0.38	N	0.333	neutral	None	None	None	None	N
A/R	0.3948	ambiguous	0.3673	ambiguous	-0.216	Destabilizing	0.38	N	0.328	neutral	None	None	None	None	N
A/S	0.1114	likely_benign	0.0956	benign	-0.565	Destabilizing	None	N	0.253	neutral	N	0.42949438	None	None	N
A/T	0.1048	likely_benign	0.0773	benign	-0.603	Destabilizing	None	N	0.181	neutral	N	0.435150916	None	None	N
A/V	0.1578	likely_benign	0.1217	benign	-0.249	Destabilizing	0.062	N	0.281	neutral	N	0.468706129	None	None	N
A/W	0.7759	likely_pathogenic	0.7371	pathogenic	-0.941	Destabilizing	0.935	D	0.554	neutral	None	None	None	None	N
A/Y	0.5442	ambiguous	0.4907	ambiguous	-0.593	Destabilizing	0.555	D	0.423	neutral	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.