TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32348	97267;97268;97269	chr2:178542812;178542811;178542810	chr2:179407539;179407538;179407537
N2AB	30707	92344;92345;92346	chr2:178542812;178542811;178542810	chr2:179407539;179407538;179407537
N2A	29780	89563;89564;89565	chr2:178542812;178542811;178542810	chr2:179407539;179407538;179407537
N2B	23283	70072;70073;70074	chr2:178542812;178542811;178542810	chr2:179407539;179407538;179407537
Novex-1	23408	70447;70448;70449	chr2:178542812;178542811;178542810	chr2:179407539;179407538;179407537
Novex-2	23475	70648;70649;70650	chr2:178542812;178542811;178542810	chr2:179407539;179407538;179407537
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-154
• Domain position: 42
• Structural Position: 69
• Q(SASA): 0.7451
• 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
R/K	None	None	None	N	0.222	0.076	0.18274738541	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.318	likely_benign	0.2666	benign	0.053	Stabilizing	0.035	N	0.483	neutral	None	None	None	None	N
R/C	0.2619	likely_benign	0.2213	benign	-0.268	Destabilizing	0.935	D	0.48	neutral	None	None	None	None	N
R/D	0.6392	likely_pathogenic	0.5892	pathogenic	-0.256	Destabilizing	0.149	N	0.467	neutral	None	None	None	None	N
R/E	0.3423	ambiguous	0.3076	benign	-0.217	Destabilizing	0.035	N	0.492	neutral	None	None	None	None	N
R/F	0.5421	ambiguous	0.4914	ambiguous	-0.289	Destabilizing	0.791	D	0.473	neutral	None	None	None	None	N
R/G	0.2303	likely_benign	0.1813	benign	-0.078	Destabilizing	0.117	N	0.505	neutral	N	0.461679448	None	None	N
R/H	0.1265	likely_benign	0.1165	benign	-0.566	Destabilizing	0.555	D	0.474	neutral	None	None	None	None	N
R/I	0.2426	likely_benign	0.2241	benign	0.348	Stabilizing	0.484	N	0.479	neutral	N	0.471549725	None	None	N
R/K	0.0837	likely_benign	0.0718	benign	-0.156	Destabilizing	None	N	0.222	neutral	N	0.392990154	None	None	N
R/L	0.217	likely_benign	0.1886	benign	0.348	Stabilizing	0.149	N	0.505	neutral	None	None	None	None	N
R/M	0.2458	likely_benign	0.2143	benign	-0.098	Destabilizing	0.791	D	0.464	neutral	None	None	None	None	N
R/N	0.5207	ambiguous	0.4636	ambiguous	-0.101	Destabilizing	0.149	N	0.493	neutral	None	None	None	None	N
R/P	0.3696	ambiguous	0.2921	benign	0.267	Stabilizing	0.555	D	0.459	neutral	None	None	None	None	N
R/Q	0.1075	likely_benign	0.0976	benign	-0.12	Destabilizing	0.081	N	0.53	neutral	None	None	None	None	N
R/S	0.4281	ambiguous	0.3734	ambiguous	-0.269	Destabilizing	0.062	N	0.514	neutral	N	0.430316392	None	None	N
R/T	0.2005	likely_benign	0.174	benign	-0.128	Destabilizing	0.117	N	0.515	neutral	N	0.436762361	None	None	N
R/V	0.2839	likely_benign	0.2604	benign	0.267	Stabilizing	0.38	N	0.433	neutral	None	None	None	None	N
R/W	0.2076	likely_benign	0.1736	benign	-0.493	Destabilizing	0.935	D	0.532	neutral	None	None	None	None	N
R/Y	0.435	ambiguous	0.3892	ambiguous	-0.082	Destabilizing	0.791	D	0.483	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.