TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27016	81271;81272;81273	chr2:178565086;178565085;178565084	chr2:179429813;179429812;179429811
N2AB	25375	76348;76349;76350	chr2:178565086;178565085;178565084	chr2:179429813;179429812;179429811
N2A	24448	73567;73568;73569	chr2:178565086;178565085;178565084	chr2:179429813;179429812;179429811
N2B	17951	54076;54077;54078	chr2:178565086;178565085;178565084	chr2:179429813;179429812;179429811
Novex-1	18076	54451;54452;54453	chr2:178565086;178565085;178565084	chr2:179429813;179429812;179429811
Novex-2	18143	54652;54653;54654	chr2:178565086;178565085;178565084	chr2:179429813;179429812;179429811
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-84
• Domain position: 45
• Structural Position: 54
• Q(SASA): 0.6391
• 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
T/I	None	None	0.983	N	0.417	0.325	0.365509141856	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
T/N	rs745404390	0.187	0.967	N	0.315	0.208	0.289098819767	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	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
T/A	0.0789	likely_benign	0.0701	benign	-0.215	Destabilizing	0.63	D	0.447	neutral	N	0.500914548	None	None	N
T/C	0.5866	likely_pathogenic	0.4639	ambiguous	-0.325	Destabilizing	0.999	D	0.46	neutral	None	None	None	None	N
T/D	0.5149	ambiguous	0.4256	ambiguous	-0.09	Destabilizing	0.975	D	0.342	neutral	None	None	None	None	N
T/E	0.4601	ambiguous	0.3834	ambiguous	-0.188	Destabilizing	0.916	D	0.349	neutral	None	None	None	None	N
T/F	0.5407	ambiguous	0.3766	ambiguous	-0.895	Destabilizing	0.996	D	0.514	neutral	None	None	None	None	N
T/G	0.2194	likely_benign	0.1718	benign	-0.258	Destabilizing	0.845	D	0.409	neutral	None	None	None	None	N
T/H	0.4386	ambiguous	0.3349	benign	-0.472	Destabilizing	0.997	D	0.514	neutral	None	None	None	None	N
T/I	0.4506	ambiguous	0.309	benign	-0.224	Destabilizing	0.983	D	0.417	neutral	N	0.470243149	None	None	N
T/K	0.3859	ambiguous	0.3143	benign	-0.283	Destabilizing	0.845	D	0.388	neutral	None	None	None	None	N
T/L	0.1611	likely_benign	0.1178	benign	-0.224	Destabilizing	0.916	D	0.385	neutral	None	None	None	None	N
T/M	0.1342	likely_benign	0.1073	benign	-0.111	Destabilizing	0.999	D	0.42	neutral	None	None	None	None	N
T/N	0.1662	likely_benign	0.1283	benign	-0.109	Destabilizing	0.967	D	0.315	neutral	N	0.492233563	None	None	N
T/P	0.5324	ambiguous	0.4458	ambiguous	-0.199	Destabilizing	0.983	D	0.417	neutral	N	0.508168595	None	None	N
T/Q	0.3376	likely_benign	0.2709	benign	-0.337	Destabilizing	0.975	D	0.417	neutral	None	None	None	None	N
T/R	0.3487	ambiguous	0.2853	benign	-0.012	Destabilizing	0.073	N	0.298	neutral	None	None	None	None	N
T/S	0.1025	likely_benign	0.0873	benign	-0.255	Destabilizing	0.099	N	0.311	neutral	N	0.42239505	None	None	N
T/V	0.2697	likely_benign	0.1892	benign	-0.199	Destabilizing	0.916	D	0.331	neutral	None	None	None	None	N
T/W	0.8817	likely_pathogenic	0.7816	pathogenic	-0.971	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
T/Y	0.5514	ambiguous	0.4185	ambiguous	-0.659	Destabilizing	0.996	D	0.514	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.