TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24916	74971;74972;74973	chr2:178571386;178571385;178571384	chr2:179436113;179436112;179436111
N2AB	23275	70048;70049;70050	chr2:178571386;178571385;178571384	chr2:179436113;179436112;179436111
N2A	22348	67267;67268;67269	chr2:178571386;178571385;178571384	chr2:179436113;179436112;179436111
N2B	15851	47776;47777;47778	chr2:178571386;178571385;178571384	chr2:179436113;179436112;179436111
Novex-1	15976	48151;48152;48153	chr2:178571386;178571385;178571384	chr2:179436113;179436112;179436111
Novex-2	16043	48352;48353;48354	chr2:178571386;178571385;178571384	chr2:179436113;179436112;179436111
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-69
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4074
• 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
V/I	rs764600357	-0.308	None	N	0.115	0.068	0.139678290688	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
V/I	rs764600357	-0.308	None	N	0.115	0.068	0.139678290688	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

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
V/A	0.0993	likely_benign	0.0972	benign	-1.296	Destabilizing	None	N	0.126	neutral	N	0.455950263	None	None	N
V/C	0.3149	likely_benign	0.3026	benign	-0.92	Destabilizing	0.628	D	0.487	neutral	None	None	None	None	N
V/D	0.2322	likely_benign	0.2212	benign	-1.024	Destabilizing	0.106	N	0.589	neutral	N	0.494911296	None	None	N
V/E	0.1761	likely_benign	0.1692	benign	-0.965	Destabilizing	0.136	N	0.504	neutral	None	None	None	None	N
V/F	0.0567	likely_benign	0.0538	benign	-0.826	Destabilizing	None	N	0.163	neutral	N	0.431497322	None	None	N
V/G	0.152	likely_benign	0.1494	benign	-1.666	Destabilizing	0.029	N	0.435	neutral	N	0.489697477	None	None	N
V/H	0.1831	likely_benign	0.1834	benign	-1.18	Destabilizing	0.214	N	0.501	neutral	None	None	None	None	N
V/I	0.0645	likely_benign	0.0655	benign	-0.365	Destabilizing	None	N	0.115	neutral	N	0.475056099	None	None	N
V/K	0.1689	likely_benign	0.1726	benign	-1.08	Destabilizing	0.072	N	0.502	neutral	None	None	None	None	N
V/L	0.0892	likely_benign	0.0976	benign	-0.365	Destabilizing	None	N	0.085	neutral	N	0.462030873	None	None	N
V/M	0.0821	likely_benign	0.0849	benign	-0.362	Destabilizing	0.007	N	0.286	neutral	None	None	None	None	N
V/N	0.1322	likely_benign	0.1366	benign	-1.038	Destabilizing	0.356	N	0.577	neutral	None	None	None	None	N
V/P	0.795	likely_pathogenic	0.7982	pathogenic	-0.64	Destabilizing	0.356	N	0.604	neutral	None	None	None	None	N
V/Q	0.1307	likely_benign	0.132	benign	-1.09	Destabilizing	0.356	N	0.599	neutral	None	None	None	None	N
V/R	0.1324	likely_benign	0.1301	benign	-0.688	Destabilizing	0.356	N	0.583	neutral	None	None	None	None	N
V/S	0.1	likely_benign	0.0952	benign	-1.614	Destabilizing	0.016	N	0.414	neutral	None	None	None	None	N
V/T	0.0954	likely_benign	0.0953	benign	-1.428	Destabilizing	0.031	N	0.277	neutral	None	None	None	None	N
V/W	0.3174	likely_benign	0.3188	benign	-1.095	Destabilizing	0.356	N	0.493	neutral	None	None	None	None	N
V/Y	0.1645	likely_benign	0.16	benign	-0.742	Destabilizing	None	N	0.171	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.