TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33543	100852;100853;100854	chr2:178536120;178536119;178536118	chr2:179400847;179400846;179400845
N2AB	31902	95929;95930;95931	chr2:178536120;178536119;178536118	chr2:179400847;179400846;179400845
N2A	30975	93148;93149;93150	chr2:178536120;178536119;178536118	chr2:179400847;179400846;179400845
N2B	24478	73657;73658;73659	chr2:178536120;178536119;178536118	chr2:179400847;179400846;179400845
Novex-1	24603	74032;74033;74034	chr2:178536120;178536119;178536118	chr2:179400847;179400846;179400845
Novex-2	24670	74233;74234;74235	chr2:178536120;178536119;178536118	chr2:179400847;179400846;179400845
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-158
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.1797
• 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
Y/H	None	None	0.994	D	0.528	0.451	0.488477830397	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85896E-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
Y/A	0.8592	likely_pathogenic	0.8919	pathogenic	-2.984	Highly Destabilizing	0.747	D	0.405	neutral	None	None	None	None	N
Y/C	0.2691	likely_benign	0.3225	benign	-1.979	Destabilizing	0.998	D	0.546	neutral	N	0.508511207	None	None	N
Y/D	0.9008	likely_pathogenic	0.8978	pathogenic	-3.096	Highly Destabilizing	0.993	D	0.593	neutral	D	0.535516232	None	None	N
Y/E	0.9408	likely_pathogenic	0.9429	pathogenic	-2.915	Highly Destabilizing	0.985	D	0.517	neutral	None	None	None	None	N
Y/F	0.118	likely_benign	0.1545	benign	-1.111	Destabilizing	0.549	D	0.447	neutral	N	0.495021231	None	None	N
Y/G	0.8542	likely_pathogenic	0.8519	pathogenic	-3.404	Highly Destabilizing	0.985	D	0.543	neutral	None	None	None	None	N
Y/H	0.5219	ambiguous	0.5535	ambiguous	-1.964	Destabilizing	0.994	D	0.528	neutral	D	0.528557801	None	None	N
Y/I	0.4131	ambiguous	0.5509	ambiguous	-1.613	Destabilizing	0.001	N	0.235	neutral	None	None	None	None	N
Y/K	0.9331	likely_pathogenic	0.9286	pathogenic	-2.255	Highly Destabilizing	0.889	D	0.528	neutral	None	None	None	None	N
Y/L	0.5271	ambiguous	0.6222	pathogenic	-1.613	Destabilizing	0.047	N	0.327	neutral	None	None	None	None	N
Y/M	0.6851	likely_pathogenic	0.781	pathogenic	-1.38	Destabilizing	0.972	D	0.527	neutral	None	None	None	None	N
Y/N	0.5884	likely_pathogenic	0.6078	pathogenic	-2.977	Highly Destabilizing	0.998	D	0.572	neutral	N	0.505802182	None	None	N
Y/P	0.9807	likely_pathogenic	0.9832	pathogenic	-2.081	Highly Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
Y/Q	0.8916	likely_pathogenic	0.8967	pathogenic	-2.748	Highly Destabilizing	0.995	D	0.541	neutral	None	None	None	None	N
Y/R	0.888	likely_pathogenic	0.8722	pathogenic	-1.946	Destabilizing	0.99	D	0.568	neutral	None	None	None	None	N
Y/S	0.7295	likely_pathogenic	0.7574	pathogenic	-3.379	Highly Destabilizing	0.98	D	0.498	neutral	D	0.533118259	None	None	N
Y/T	0.7312	likely_pathogenic	0.7838	pathogenic	-3.076	Highly Destabilizing	0.931	D	0.44	neutral	None	None	None	None	N
Y/V	0.3448	ambiguous	0.4624	ambiguous	-2.081	Highly Destabilizing	0.014	N	0.234	neutral	None	None	None	None	N
Y/W	0.5821	likely_pathogenic	0.6027	pathogenic	-0.541	Destabilizing	0.997	D	0.533	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.