TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8537	25834;25835;25836	chr2:178717125;178717124;178717123	chr2:179581852;179581851;179581850
N2AB	8220	24883;24884;24885	chr2:178717125;178717124;178717123	chr2:179581852;179581851;179581850
N2A	7293	22102;22103;22104	chr2:178717125;178717124;178717123	chr2:179581852;179581851;179581850
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-70
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1302
• 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
D/E	None	None	0.063	N	0.345	0.072	0.333154297509	gnomAD-4.0.0	1.36895E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.3151E-05
D/N	rs2077605401	None	0.993	N	0.581	0.337	0.513112959101	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
D/A	0.1985	likely_benign	0.2052	benign	-0.533	Destabilizing	0.978	D	0.609	neutral	N	0.441224032	None	None	I
D/C	0.8675	likely_pathogenic	0.8882	pathogenic	-0.237	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
D/E	0.3536	ambiguous	0.3502	ambiguous	-0.44	Destabilizing	0.063	N	0.345	neutral	N	0.491460851	None	None	I
D/F	0.7796	likely_pathogenic	0.79	pathogenic	0.153	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
D/G	0.2754	likely_benign	0.293	benign	-0.906	Destabilizing	0.985	D	0.618	neutral	N	0.505749276	None	None	I
D/H	0.5817	likely_pathogenic	0.6206	pathogenic	-0.057	Destabilizing	1.0	D	0.62	neutral	N	0.505749276	None	None	I
D/I	0.5868	likely_pathogenic	0.6115	pathogenic	0.462	Stabilizing	0.997	D	0.675	neutral	None	None	None	None	I
D/K	0.7434	likely_pathogenic	0.7566	pathogenic	-0.196	Destabilizing	0.995	D	0.61	neutral	None	None	None	None	I
D/L	0.6624	likely_pathogenic	0.681	pathogenic	0.462	Stabilizing	0.991	D	0.663	neutral	None	None	None	None	I
D/M	0.8242	likely_pathogenic	0.8406	pathogenic	0.783	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
D/N	0.177	likely_benign	0.2078	benign	-0.773	Destabilizing	0.993	D	0.581	neutral	N	0.493379012	None	None	I
D/P	0.9822	likely_pathogenic	0.9854	pathogenic	0.155	Stabilizing	0.989	D	0.653	neutral	None	None	None	None	I
D/Q	0.6137	likely_pathogenic	0.6276	pathogenic	-0.612	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	I
D/R	0.7731	likely_pathogenic	0.7865	pathogenic	0.036	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
D/S	0.1956	likely_benign	0.2168	benign	-1.038	Destabilizing	0.967	D	0.531	neutral	None	None	None	None	I
D/T	0.3919	ambiguous	0.4011	ambiguous	-0.72	Destabilizing	0.448	N	0.355	neutral	None	None	None	None	I
D/V	0.315	likely_benign	0.3273	benign	0.155	Stabilizing	0.463	N	0.523	neutral	N	0.470122786	None	None	I
D/W	0.9746	likely_pathogenic	0.9779	pathogenic	0.434	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
D/Y	0.4106	ambiguous	0.4296	ambiguous	0.438	Stabilizing	1.0	D	0.72	prob.delet.	N	0.5097882	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.