TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24720	74383;74384;74385	chr2:178571974;178571973;178571972	chr2:179436701;179436700;179436699
N2AB	23079	69460;69461;69462	chr2:178571974;178571973;178571972	chr2:179436701;179436700;179436699
N2A	22152	66679;66680;66681	chr2:178571974;178571973;178571972	chr2:179436701;179436700;179436699
N2B	15655	47188;47189;47190	chr2:178571974;178571973;178571972	chr2:179436701;179436700;179436699
Novex-1	15780	47563;47564;47565	chr2:178571974;178571973;178571972	chr2:179436701;179436700;179436699
Novex-2	15847	47764;47765;47766	chr2:178571974;178571973;178571972	chr2:179436701;179436700;179436699
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-133
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4821
• 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
L/F	None	None	0.997	N	0.511	0.404	0.710867761551	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
L/A	0.5463	ambiguous	0.5197	ambiguous	-1.705	Destabilizing	0.992	D	0.436	neutral	None	None	None	None	N
L/C	0.6492	likely_pathogenic	0.6503	pathogenic	-1.171	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
L/D	0.9055	likely_pathogenic	0.9064	pathogenic	-1.34	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
L/E	0.7468	likely_pathogenic	0.7452	pathogenic	-1.211	Destabilizing	0.995	D	0.635	neutral	None	None	None	None	N
L/F	0.3017	likely_benign	0.2699	benign	-0.939	Destabilizing	0.997	D	0.511	neutral	N	0.498632478	None	None	N
L/G	0.7605	likely_pathogenic	0.7514	pathogenic	-2.103	Highly Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
L/H	0.4935	ambiguous	0.4839	ambiguous	-1.142	Destabilizing	1.0	D	0.649	neutral	N	0.500600409	None	None	N
L/I	0.141	likely_benign	0.1354	benign	-0.622	Destabilizing	0.978	D	0.36	neutral	N	0.486727035	None	None	N
L/K	0.5514	ambiguous	0.5554	ambiguous	-1.242	Destabilizing	0.995	D	0.563	neutral	None	None	None	None	N
L/M	0.137	likely_benign	0.1329	benign	-0.714	Destabilizing	0.96	D	0.285	neutral	None	None	None	None	N
L/N	0.6379	likely_pathogenic	0.6367	pathogenic	-1.423	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
L/P	0.3986	ambiguous	0.384	ambiguous	-0.958	Destabilizing	0.999	D	0.69	prob.neutral	N	0.508950533	None	None	N
L/Q	0.4048	ambiguous	0.3911	ambiguous	-1.39	Destabilizing	0.96	D	0.353	neutral	None	None	None	None	N
L/R	0.4754	ambiguous	0.47	ambiguous	-0.866	Destabilizing	0.997	D	0.657	neutral	N	0.514393639	None	None	N
L/S	0.6662	likely_pathogenic	0.6371	pathogenic	-2.053	Highly Destabilizing	0.998	D	0.564	neutral	None	None	None	None	N
L/T	0.4657	ambiguous	0.4535	ambiguous	-1.785	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	N
L/V	0.1464	likely_benign	0.1388	benign	-0.958	Destabilizing	0.978	D	0.373	neutral	D	0.524418631	None	None	N
L/W	0.5557	ambiguous	0.5165	ambiguous	-1.083	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
L/Y	0.5606	ambiguous	0.5455	ambiguous	-0.818	Destabilizing	1.0	D	0.593	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.