TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28677	86254;86255;86256	chr2:178560103;178560102;178560101	chr2:179424830;179424829;179424828
N2AB	27036	81331;81332;81333	chr2:178560103;178560102;178560101	chr2:179424830;179424829;179424828
N2A	26109	78550;78551;78552	chr2:178560103;178560102;178560101	chr2:179424830;179424829;179424828
N2B	19612	59059;59060;59061	chr2:178560103;178560102;178560101	chr2:179424830;179424829;179424828
Novex-1	19737	59434;59435;59436	chr2:178560103;178560102;178560101	chr2:179424830;179424829;179424828
Novex-2	19804	59635;59636;59637	chr2:178560103;178560102;178560101	chr2:179424830;179424829;179424828
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-97
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.523
• 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
F/S	rs1553561985	None	0.983	N	0.585	0.396	0.61589852972	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62502E-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
F/A	0.9597	likely_pathogenic	0.9157	pathogenic	-1.048	Destabilizing	0.916	D	0.467	neutral	None	None	None	None	I
F/C	0.8944	likely_pathogenic	0.8129	pathogenic	-0.34	Destabilizing	0.999	D	0.613	neutral	N	0.469021246	None	None	I
F/D	0.9798	likely_pathogenic	0.9636	pathogenic	0.917	Stabilizing	0.996	D	0.649	neutral	None	None	None	None	I
F/E	0.9837	likely_pathogenic	0.9713	pathogenic	0.899	Stabilizing	0.987	D	0.651	neutral	None	None	None	None	I
F/G	0.9736	likely_pathogenic	0.9546	pathogenic	-1.246	Destabilizing	0.987	D	0.631	neutral	None	None	None	None	I
F/H	0.8526	likely_pathogenic	0.7854	pathogenic	0.179	Stabilizing	0.975	D	0.549	neutral	None	None	None	None	I
F/I	0.9213	likely_pathogenic	0.8321	pathogenic	-0.544	Destabilizing	0.967	D	0.484	neutral	N	0.463398932	None	None	I
F/K	0.9775	likely_pathogenic	0.9691	pathogenic	-0.073	Destabilizing	0.987	D	0.654	neutral	None	None	None	None	I
F/L	0.9905	likely_pathogenic	0.9807	pathogenic	-0.544	Destabilizing	0.805	D	0.453	neutral	N	0.477648113	None	None	I
F/M	0.9365	likely_pathogenic	0.8863	pathogenic	-0.361	Destabilizing	0.999	D	0.512	neutral	None	None	None	None	I
F/N	0.9399	likely_pathogenic	0.8889	pathogenic	0.007	Stabilizing	0.987	D	0.657	neutral	None	None	None	None	I
F/P	0.9987	likely_pathogenic	0.9982	pathogenic	-0.692	Destabilizing	0.996	D	0.644	neutral	None	None	None	None	I
F/Q	0.9583	likely_pathogenic	0.9324	pathogenic	-0.07	Destabilizing	0.987	D	0.647	neutral	None	None	None	None	I
F/R	0.9386	likely_pathogenic	0.9181	pathogenic	0.423	Stabilizing	0.987	D	0.651	neutral	None	None	None	None	I
F/S	0.9101	likely_pathogenic	0.8036	pathogenic	-0.746	Destabilizing	0.983	D	0.585	neutral	N	0.448037282	None	None	I
F/T	0.9439	likely_pathogenic	0.8893	pathogenic	-0.675	Destabilizing	0.987	D	0.589	neutral	None	None	None	None	I
F/V	0.9053	likely_pathogenic	0.8078	pathogenic	-0.692	Destabilizing	0.892	D	0.516	neutral	N	0.507354944	None	None	I
F/W	0.7689	likely_pathogenic	0.7087	pathogenic	-0.259	Destabilizing	0.997	D	0.502	neutral	None	None	None	None	I
F/Y	0.2874	likely_benign	0.2398	benign	-0.242	Destabilizing	0.025	N	0.28	neutral	N	0.426451288	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.