TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27233	81922;81923;81924	chr2:178564435;178564434;178564433	chr2:179429162;179429161;179429160
N2AB	25592	76999;77000;77001	chr2:178564435;178564434;178564433	chr2:179429162;179429161;179429160
N2A	24665	74218;74219;74220	chr2:178564435;178564434;178564433	chr2:179429162;179429161;179429160
N2B	18168	54727;54728;54729	chr2:178564435;178564434;178564433	chr2:179429162;179429161;179429160
Novex-1	18293	55102;55103;55104	chr2:178564435;178564434;178564433	chr2:179429162;179429161;179429160
Novex-2	18360	55303;55304;55305	chr2:178564435;178564434;178564433	chr2:179429162;179429161;179429160
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-86
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.5572
• 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
S/N	None	None	0.117	N	0.418	0.101	0.18274738541	gnomAD-4.0.0	1.59359E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41196E-04	0	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
S/A	0.0947	likely_benign	0.0883	benign	-0.511	Destabilizing	0.001	N	0.177	neutral	None	None	None	None	N
S/C	0.1683	likely_benign	0.1576	benign	-0.338	Destabilizing	0.78	D	0.541	neutral	N	0.485032949	None	None	N
S/D	0.588	likely_pathogenic	0.5092	ambiguous	0.094	Stabilizing	0.149	N	0.383	neutral	None	None	None	None	N
S/E	0.6989	likely_pathogenic	0.6491	pathogenic	0.018	Stabilizing	0.149	N	0.369	neutral	None	None	None	None	N
S/F	0.3475	ambiguous	0.2828	benign	-0.995	Destabilizing	0.555	D	0.625	neutral	None	None	None	None	N
S/G	0.1114	likely_benign	0.1052	benign	-0.658	Destabilizing	0.052	N	0.391	neutral	N	0.501397338	None	None	N
S/H	0.5291	ambiguous	0.4756	ambiguous	-1.118	Destabilizing	0.935	D	0.541	neutral	None	None	None	None	N
S/I	0.2937	likely_benign	0.2462	benign	-0.247	Destabilizing	0.188	N	0.602	neutral	N	0.507843308	None	None	N
S/K	0.8174	likely_pathogenic	0.7562	pathogenic	-0.585	Destabilizing	0.149	N	0.361	neutral	None	None	None	None	N
S/L	0.1205	likely_benign	0.1034	benign	-0.247	Destabilizing	0.081	N	0.515	neutral	None	None	None	None	N
S/M	0.2123	likely_benign	0.1818	benign	0.006	Stabilizing	0.555	D	0.549	neutral	None	None	None	None	N
S/N	0.1899	likely_benign	0.1588	benign	-0.323	Destabilizing	0.117	N	0.418	neutral	N	0.492911141	None	None	N
S/P	0.2323	likely_benign	0.1993	benign	-0.305	Destabilizing	0.555	D	0.553	neutral	None	None	None	None	N
S/Q	0.6584	likely_pathogenic	0.6111	pathogenic	-0.557	Destabilizing	0.555	D	0.465	neutral	None	None	None	None	N
S/R	0.8019	likely_pathogenic	0.7381	pathogenic	-0.362	Destabilizing	0.317	N	0.565	neutral	N	0.487697322	None	None	N
S/T	0.0652	likely_benign	0.0588	benign	-0.427	Destabilizing	None	N	0.174	neutral	N	0.367733845	None	None	N
S/V	0.2685	likely_benign	0.2281	benign	-0.305	Destabilizing	0.081	N	0.51	neutral	None	None	None	None	N
S/W	0.5522	ambiguous	0.4875	ambiguous	-0.976	Destabilizing	0.935	D	0.635	neutral	None	None	None	None	N
S/Y	0.3433	ambiguous	0.2841	benign	-0.713	Destabilizing	0.555	D	0.621	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.