TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30678	92257;92258;92259	chr2:178549690;178549689;178549688	chr2:179414417;179414416;179414415
N2AB	29037	87334;87335;87336	chr2:178549690;178549689;178549688	chr2:179414417;179414416;179414415
N2A	28110	84553;84554;84555	chr2:178549690;178549689;178549688	chr2:179414417;179414416;179414415
N2B	21613	65062;65063;65064	chr2:178549690;178549689;178549688	chr2:179414417;179414416;179414415
Novex-1	21738	65437;65438;65439	chr2:178549690;178549689;178549688	chr2:179414417;179414416;179414415
Novex-2	21805	65638;65639;65640	chr2:178549690;178549689;178549688	chr2:179414417;179414416;179414415
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: Fn3-111
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2059
• 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	0.822	N	0.547	0.179	0.151104730317	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02407E-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	0.1052	likely_benign	0.1197	benign	-0.311	Destabilizing	0.559	D	0.477	neutral	None	None	None	None	N
S/C	0.1181	likely_benign	0.1318	benign	0.076	Stabilizing	0.997	D	0.7	prob.neutral	N	0.49045468	None	None	N
S/D	0.6563	likely_pathogenic	0.7407	pathogenic	-0.521	Destabilizing	0.86	D	0.545	neutral	None	None	None	None	N
S/E	0.6656	likely_pathogenic	0.7274	pathogenic	-0.348	Destabilizing	0.86	D	0.511	neutral	None	None	None	None	N
S/F	0.2527	likely_benign	0.325	benign	-0.312	Destabilizing	0.978	D	0.761	deleterious	None	None	None	None	N
S/G	0.1378	likely_benign	0.1599	benign	-0.685	Destabilizing	0.822	D	0.496	neutral	N	0.486224718	None	None	N
S/H	0.3887	ambiguous	0.421	ambiguous	-1.012	Destabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	N
S/I	0.2318	likely_benign	0.2739	benign	0.623	Stabilizing	0.942	D	0.738	prob.delet.	N	0.484098351	None	None	N
S/K	0.7498	likely_pathogenic	0.8132	pathogenic	0.312	Stabilizing	0.754	D	0.493	neutral	None	None	None	None	N
S/L	0.1511	likely_benign	0.1844	benign	0.623	Stabilizing	0.754	D	0.633	neutral	None	None	None	None	N
S/M	0.21	likely_benign	0.2192	benign	0.424	Stabilizing	0.994	D	0.699	prob.neutral	None	None	None	None	N
S/N	0.1725	likely_benign	0.1913	benign	-0.269	Destabilizing	0.822	D	0.547	neutral	N	0.462476377	None	None	N
S/P	0.8929	likely_pathogenic	0.9218	pathogenic	0.347	Stabilizing	0.978	D	0.695	prob.neutral	None	None	None	None	N
S/Q	0.5231	ambiguous	0.567	pathogenic	-0.041	Destabilizing	0.956	D	0.595	neutral	None	None	None	None	N
S/R	0.6527	likely_pathogenic	0.753	pathogenic	-0.083	Destabilizing	0.032	N	0.356	neutral	N	0.476520323	None	None	N
S/T	0.0927	likely_benign	0.1034	benign	-0.015	Destabilizing	0.014	N	0.404	neutral	N	0.429958527	None	None	N
S/V	0.2271	likely_benign	0.2648	benign	0.347	Stabilizing	0.915	D	0.667	neutral	None	None	None	None	N
S/W	0.4311	ambiguous	0.5105	ambiguous	-0.608	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
S/Y	0.2066	likely_benign	0.2534	benign	-0.08	Destabilizing	0.993	D	0.759	deleterious	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.