TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6700	20323;20324;20325	chr2:178727267;178727266;178727265	chr2:179591994;179591993;179591992
N2AB	6383	19372;19373;19374	chr2:178727267;178727266;178727265	chr2:179591994;179591993;179591992
N2A	5456	16591;16592;16593	chr2:178727267;178727266;178727265	chr2:179591994;179591993;179591992
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-51
• Domain position: 34
• Structural Position: 47
• Q(SASA): 0.2725
• 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/A	rs367635778	None	0.005	N	0.322	0.074	0.468753983522	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
V/A	rs367635778	None	0.005	N	0.322	0.074	0.468753983522	gnomAD-4.0.0	3.7196E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08718E-06	0	0
V/L	rs72648957	-0.336	0.004	N	0.368	0.114	0.326074293725	gnomAD-4.0.0	1.5928E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.861E-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	0.0971	likely_benign	0.1082	benign	-1.677	Destabilizing	0.005	N	0.322	neutral	N	0.474240527	None	None	N
V/C	0.6104	likely_pathogenic	0.6134	pathogenic	-0.868	Destabilizing	0.676	D	0.521	neutral	None	None	None	None	N
V/D	0.2106	likely_benign	0.2293	benign	-2.025	Highly Destabilizing	0.072	N	0.558	neutral	None	None	None	None	N
V/E	0.1507	likely_benign	0.1727	benign	-1.902	Destabilizing	0.024	N	0.495	neutral	N	0.464330178	None	None	N
V/F	0.1054	likely_benign	0.1105	benign	-1.061	Destabilizing	0.214	N	0.556	neutral	None	None	None	None	N
V/G	0.1425	likely_benign	0.1498	benign	-2.101	Highly Destabilizing	None	N	0.458	neutral	N	0.517300658	None	None	N
V/H	0.2344	likely_benign	0.2658	benign	-1.807	Destabilizing	0.356	N	0.565	neutral	None	None	None	None	N
V/I	0.0754	likely_benign	0.0754	benign	-0.545	Destabilizing	0.016	N	0.435	neutral	None	None	None	None	N
V/K	0.1114	likely_benign	0.1367	benign	-1.4	Destabilizing	0.001	N	0.384	neutral	None	None	None	None	N
V/L	0.108	likely_benign	0.1152	benign	-0.545	Destabilizing	0.004	N	0.368	neutral	N	0.440976102	None	None	N
V/M	0.0903	likely_benign	0.0973	benign	-0.349	Destabilizing	0.002	N	0.348	neutral	N	0.506603662	None	None	N
V/N	0.1316	likely_benign	0.1433	benign	-1.399	Destabilizing	0.072	N	0.558	neutral	None	None	None	None	N
V/P	0.8537	likely_pathogenic	0.8786	pathogenic	-0.893	Destabilizing	0.136	N	0.586	neutral	None	None	None	None	N
V/Q	0.1244	likely_benign	0.1438	benign	-1.414	Destabilizing	0.072	N	0.588	neutral	None	None	None	None	N
V/R	0.092	likely_benign	0.1096	benign	-1.044	Destabilizing	None	N	0.469	neutral	None	None	None	None	N
V/S	0.0906	likely_benign	0.099	benign	-1.919	Destabilizing	0.001	N	0.382	neutral	None	None	None	None	N
V/T	0.0844	likely_benign	0.0944	benign	-1.686	Destabilizing	None	N	0.241	neutral	None	None	None	None	N
V/W	0.5397	ambiguous	0.5833	pathogenic	-1.51	Destabilizing	0.864	D	0.583	neutral	None	None	None	None	N
V/Y	0.3301	likely_benign	0.3527	ambiguous	-1.125	Destabilizing	0.356	N	0.542	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.