TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22529	67810;67811;67812	chr2:178579612;178579611;178579610	chr2:179444339;179444338;179444337
N2AB	20888	62887;62888;62889	chr2:178579612;178579611;178579610	chr2:179444339;179444338;179444337
N2A	19961	60106;60107;60108	chr2:178579612;178579611;178579610	chr2:179444339;179444338;179444337
N2B	13464	40615;40616;40617	chr2:178579612;178579611;178579610	chr2:179444339;179444338;179444337
Novex-1	13589	40990;40991;40992	chr2:178579612;178579611;178579610	chr2:179444339;179444338;179444337
Novex-2	13656	41191;41192;41193	chr2:178579612;178579611;178579610	chr2:179444339;179444338;179444337
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: Fn3-51
• Domain position: 79
• Structural Position: 114
• Q(SASA): 0.5882
• 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
N/S	None	None	0.003	N	0.17	0.156	0.202949470691	gnomAD-4.0.0	4.1062E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39796E-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
N/A	0.151	likely_benign	0.166	benign	-0.299	Destabilizing	0.001	N	0.273	neutral	None	None	None	None	I
N/C	0.1775	likely_benign	0.1797	benign	0.332	Stabilizing	0.944	D	0.533	neutral	None	None	None	None	I
N/D	0.2525	likely_benign	0.2751	benign	-0.064	Destabilizing	0.425	N	0.297	neutral	N	0.487657249	None	None	I
N/E	0.3537	ambiguous	0.4109	ambiguous	-0.127	Destabilizing	0.495	N	0.286	neutral	None	None	None	None	I
N/F	0.3092	likely_benign	0.386	ambiguous	-0.807	Destabilizing	0.944	D	0.549	neutral	None	None	None	None	I
N/G	0.2935	likely_benign	0.3121	benign	-0.417	Destabilizing	0.176	N	0.217	neutral	None	None	None	None	I
N/H	0.0916	likely_benign	0.1032	benign	-0.48	Destabilizing	0.975	D	0.344	neutral	N	0.40663895	None	None	I
N/I	0.1362	likely_benign	0.1606	benign	-0.081	Destabilizing	0.642	D	0.525	neutral	N	0.378548272	None	None	I
N/K	0.213	likely_benign	0.2531	benign	0.164	Stabilizing	0.425	N	0.286	neutral	N	0.422413692	None	None	I
N/L	0.1933	likely_benign	0.2275	benign	-0.081	Destabilizing	0.495	N	0.538	neutral	None	None	None	None	I
N/M	0.2043	likely_benign	0.2341	benign	0.321	Stabilizing	0.981	D	0.537	neutral	None	None	None	None	I
N/P	0.8965	likely_pathogenic	0.9072	pathogenic	-0.13	Destabilizing	0.828	D	0.541	neutral	None	None	None	None	I
N/Q	0.2448	likely_benign	0.2831	benign	-0.318	Destabilizing	0.828	D	0.325	neutral	None	None	None	None	I
N/R	0.2323	likely_benign	0.2767	benign	0.287	Stabilizing	0.704	D	0.255	neutral	None	None	None	None	I
N/S	0.0941	likely_benign	0.1003	benign	-0.012	Destabilizing	0.003	N	0.17	neutral	N	0.361578664	None	None	I
N/T	0.1295	likely_benign	0.1333	benign	0.045	Stabilizing	0.27	N	0.279	neutral	N	0.45881721	None	None	I
N/V	0.1475	likely_benign	0.1704	benign	-0.13	Destabilizing	0.543	D	0.515	neutral	None	None	None	None	I
N/W	0.6549	likely_pathogenic	0.7281	pathogenic	-0.831	Destabilizing	0.995	D	0.553	neutral	None	None	None	None	I
N/Y	0.0944	likely_benign	0.1091	benign	-0.549	Destabilizing	0.975	D	0.531	neutral	N	0.367389916	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.