TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9119	27580;27581;27582	chr2:178712567;178712566;178712565	chr2:179577294;179577293;179577292
N2AB	8802	26629;26630;26631	chr2:178712567;178712566;178712565	chr2:179577294;179577293;179577292
N2A	7875	23848;23849;23850	chr2:178712567;178712566;178712565	chr2:179577294;179577293;179577292
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-77
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5861
• 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
N/K	rs2154296108	None	0.028	N	0.096	0.126	0.126345400529	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/K	rs2154296108	None	0.028	N	0.096	0.126	0.126345400529	gnomAD-4.0.0	6.56607E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47016E-05	0	0
N/S	None	None	0.514	N	0.284	0.178	0.180583059064	gnomAD-4.0.0	1.36946E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7999E-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
N/A	0.1526	likely_benign	0.1528	benign	-0.289	Destabilizing	0.737	D	0.334	neutral	None	None	None	None	N
N/C	0.2751	likely_benign	0.2484	benign	0.18	Stabilizing	0.998	D	0.425	neutral	None	None	None	None	N
N/D	0.1406	likely_benign	0.1375	benign	0.242	Stabilizing	0.837	D	0.227	neutral	N	0.50583287	None	None	N
N/E	0.2794	likely_benign	0.2794	benign	0.223	Stabilizing	0.584	D	0.26	neutral	None	None	None	None	N
N/F	0.4052	ambiguous	0.3959	ambiguous	-0.714	Destabilizing	0.993	D	0.446	neutral	None	None	None	None	N
N/G	0.1982	likely_benign	0.1912	benign	-0.455	Destabilizing	0.85	D	0.225	neutral	None	None	None	None	N
N/H	0.0944	likely_benign	0.0877	benign	-0.372	Destabilizing	0.973	D	0.344	neutral	N	0.506526304	None	None	N
N/I	0.1624	likely_benign	0.1654	benign	0.06	Stabilizing	0.947	D	0.448	neutral	N	0.487111588	None	None	N
N/K	0.1912	likely_benign	0.1869	benign	0.153	Stabilizing	0.028	N	0.096	neutral	N	0.419480535	None	None	N
N/L	0.1745	likely_benign	0.1704	benign	0.06	Stabilizing	0.872	D	0.39	neutral	None	None	None	None	N
N/M	0.2404	likely_benign	0.2393	benign	0.12	Stabilizing	0.993	D	0.416	neutral	None	None	None	None	N
N/P	0.4155	ambiguous	0.3912	ambiguous	-0.03	Destabilizing	0.993	D	0.426	neutral	None	None	None	None	N
N/Q	0.2269	likely_benign	0.2203	benign	-0.275	Destabilizing	0.209	N	0.177	neutral	None	None	None	None	N
N/R	0.2219	likely_benign	0.2067	benign	0.214	Stabilizing	0.021	N	0.1	neutral	None	None	None	None	N
N/S	0.068	likely_benign	0.0693	benign	-0.134	Destabilizing	0.514	D	0.284	neutral	N	0.398761333	None	None	N
N/T	0.0881	likely_benign	0.0926	benign	-0.004	Destabilizing	0.064	N	0.111	neutral	N	0.442264181	None	None	N
N/V	0.1793	likely_benign	0.1807	benign	-0.03	Destabilizing	0.872	D	0.41	neutral	None	None	None	None	N
N/W	0.6584	likely_pathogenic	0.611	pathogenic	-0.745	Destabilizing	0.998	D	0.459	neutral	None	None	None	None	N
N/Y	0.1423	likely_benign	0.1313	benign	-0.442	Destabilizing	0.991	D	0.435	neutral	N	0.487365078	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.