TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7316	22171;22172;22173	chr2:178723061;178723060;178723059	chr2:179587788;179587787;179587786
N2AB	6999	21220;21221;21222	chr2:178723061;178723060;178723059	chr2:179587788;179587787;179587786
N2A	6072	18439;18440;18441	chr2:178723061;178723060;178723059	chr2:179587788;179587787;179587786
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-57
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3829
• 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/R	rs745745237	0.191	0.272	N	0.562	0.164	0.505640481493	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/R	rs745745237	0.191	0.272	N	0.562	0.164	0.505640481493	gnomAD-4.0.0	6.36799E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14379E-05	0	0
L/V	None	None	None	N	0.18	0.128	0.229264304666	gnomAD-4.0.0	6.84339E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99586E-07	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
L/A	0.0992	likely_benign	0.1124	benign	-0.97	Destabilizing	0.002	N	0.257	neutral	None	None	None	None	N
L/C	0.3684	ambiguous	0.3895	ambiguous	-0.702	Destabilizing	0.859	D	0.515	neutral	None	None	None	None	N
L/D	0.2883	likely_benign	0.3331	benign	-0.334	Destabilizing	0.22	N	0.543	neutral	None	None	None	None	N
L/E	0.1373	likely_benign	0.1601	benign	-0.405	Destabilizing	0.124	N	0.507	neutral	None	None	None	None	N
L/F	0.0844	likely_benign	0.0883	benign	-0.835	Destabilizing	0.497	N	0.47	neutral	None	None	None	None	N
L/G	0.3045	likely_benign	0.3443	ambiguous	-1.189	Destabilizing	0.124	N	0.485	neutral	None	None	None	None	N
L/H	0.1088	likely_benign	0.1151	benign	-0.456	Destabilizing	0.789	D	0.513	neutral	None	None	None	None	N
L/I	0.069	likely_benign	0.0718	benign	-0.496	Destabilizing	0.02	N	0.394	neutral	None	None	None	None	N
L/K	0.117	likely_benign	0.1211	benign	-0.521	Destabilizing	0.124	N	0.5	neutral	None	None	None	None	N
L/M	0.0925	likely_benign	0.0961	benign	-0.416	Destabilizing	0.007	N	0.244	neutral	N	0.451817774	None	None	N
L/N	0.1602	likely_benign	0.1787	benign	-0.286	Destabilizing	0.22	N	0.56	neutral	None	None	None	None	N
L/P	0.3412	ambiguous	0.4259	ambiguous	-0.62	Destabilizing	0.602	D	0.566	neutral	N	0.470175518	None	None	N
L/Q	0.0775	likely_benign	0.0835	benign	-0.53	Destabilizing	0.007	N	0.314	neutral	N	0.412590983	None	None	N
L/R	0.0926	likely_benign	0.0917	benign	0.055	Stabilizing	0.272	N	0.562	neutral	N	0.436755922	None	None	N
L/S	0.1019	likely_benign	0.1175	benign	-0.82	Destabilizing	0.011	N	0.337	neutral	None	None	None	None	N
L/T	0.0908	likely_benign	0.0949	benign	-0.78	Destabilizing	0.002	N	0.237	neutral	None	None	None	None	N
L/V	0.0643	likely_benign	0.0659	benign	-0.62	Destabilizing	None	N	0.18	neutral	N	0.471580571	None	None	N
L/W	0.1525	likely_benign	0.1628	benign	-0.835	Destabilizing	0.958	D	0.539	neutral	None	None	None	None	N
L/Y	0.1956	likely_benign	0.2158	benign	-0.589	Destabilizing	0.667	D	0.535	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.