TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33049	99370;99371;99372	chr2:178538684;178538683;178538682	chr2:179403411;179403410;179403409
N2AB	31408	94447;94448;94449	chr2:178538684;178538683;178538682	chr2:179403411;179403410;179403409
N2A	30481	91666;91667;91668	chr2:178538684;178538683;178538682	chr2:179403411;179403410;179403409
N2B	23984	72175;72176;72177	chr2:178538684;178538683;178538682	chr2:179403411;179403410;179403409
Novex-1	24109	72550;72551;72552	chr2:178538684;178538683;178538682	chr2:179403411;179403410;179403409
Novex-2	24176	72751;72752;72753	chr2:178538684;178538683;178538682	chr2:179403411;179403410;179403409
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-129
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.0597
• 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
N/K	None	None	0.124	N	0.677	0.22	0.199424873507	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	0
N/S	rs1692887822	None	0.001	N	0.417	0.147	0.104622674875	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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
N/A	0.4202	ambiguous	0.6494	pathogenic	-0.982	Destabilizing	0.157	N	0.649	neutral	None	None	None	None	N
N/C	0.3292	likely_benign	0.5063	ambiguous	-0.083	Destabilizing	0.909	D	0.698	prob.neutral	None	None	None	None	N
N/D	0.447	ambiguous	0.6969	pathogenic	-0.594	Destabilizing	0.124	N	0.632	neutral	N	0.477333493	None	None	N
N/E	0.7942	likely_pathogenic	0.911	pathogenic	-0.378	Destabilizing	0.157	N	0.657	neutral	None	None	None	None	N
N/F	0.8427	likely_pathogenic	0.9377	pathogenic	-0.537	Destabilizing	0.726	D	0.692	prob.neutral	None	None	None	None	N
N/G	0.3972	ambiguous	0.5662	pathogenic	-1.388	Destabilizing	0.157	N	0.611	neutral	None	None	None	None	N
N/H	0.2751	likely_benign	0.4745	ambiguous	-0.66	Destabilizing	0.002	N	0.431	neutral	N	0.480575951	None	None	N
N/I	0.5243	ambiguous	0.7572	pathogenic	0.103	Stabilizing	0.497	N	0.698	prob.neutral	N	0.474789053	None	None	N
N/K	0.8434	likely_pathogenic	0.9404	pathogenic	0.152	Stabilizing	0.124	N	0.677	prob.neutral	N	0.492880081	None	None	N
N/L	0.4725	ambiguous	0.6779	pathogenic	0.103	Stabilizing	0.272	N	0.692	prob.neutral	None	None	None	None	N
N/M	0.6073	likely_pathogenic	0.7999	pathogenic	0.265	Stabilizing	0.968	D	0.643	neutral	None	None	None	None	N
N/P	0.7855	likely_pathogenic	0.8889	pathogenic	-0.231	Destabilizing	0.567	D	0.676	prob.neutral	None	None	None	None	N
N/Q	0.6769	likely_pathogenic	0.8332	pathogenic	-0.39	Destabilizing	0.567	D	0.682	prob.neutral	None	None	None	None	N
N/R	0.8195	likely_pathogenic	0.9153	pathogenic	0.02	Stabilizing	0.567	D	0.69	prob.neutral	None	None	None	None	N
N/S	0.0868	likely_benign	0.1287	benign	-0.893	Destabilizing	0.001	N	0.417	neutral	N	0.508840598	None	None	N
N/T	0.1542	likely_benign	0.2669	benign	-0.455	Destabilizing	0.004	N	0.444	neutral	N	0.514246418	None	None	N
N/V	0.4175	ambiguous	0.6574	pathogenic	-0.231	Destabilizing	0.567	D	0.689	prob.neutral	None	None	None	None	N
N/W	0.9398	likely_pathogenic	0.9796	pathogenic	-0.266	Destabilizing	0.968	D	0.691	prob.neutral	None	None	None	None	N
N/Y	0.5066	ambiguous	0.7394	pathogenic	0.027	Stabilizing	0.497	N	0.662	neutral	N	0.483146845	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.