TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5107	15544;15545;15546	chr2:178734505;178734504;178734503	chr2:179599232;179599231;179599230
N2AB	4790	14593;14594;14595	chr2:178734505;178734504;178734503	chr2:179599232;179599231;179599230
N2A	3863	11812;11813;11814	chr2:178734505;178734504;178734503	chr2:179599232;179599231;179599230
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-34
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2313
• 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
S/I	rs748973546	0.643	0.317	N	0.595	0.395	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.5E-05	0	None	0	0	None	0	None	0	0	0
S/I	rs748973546	0.643	0.317	N	0.595	0.395	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	4.41E-05	0	0
S/I	rs748973546	0.643	0.317	N	0.595	0.395	None	gnomAD-4.0.0	2.72695E-05	None	None	None	None	N	None	1.33472E-05	0	None	0	0	None	0	0	3.64493E-05	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
S/A	0.0852	likely_benign	0.0958	benign	-0.468	Destabilizing	0.035	N	0.482	neutral	None	None	None	None	N
S/C	0.1009	likely_benign	0.1128	benign	-0.278	Destabilizing	0.915	D	0.584	neutral	D	0.712689511	None	None	N
S/D	0.4968	ambiguous	0.4974	ambiguous	-0.061	Destabilizing	0.081	N	0.549	neutral	None	None	None	None	N
S/E	0.6171	likely_pathogenic	0.5921	pathogenic	0.015	Stabilizing	0.081	N	0.546	neutral	None	None	None	None	N
S/F	0.2067	likely_benign	0.2453	benign	-0.594	Destabilizing	0.555	D	0.601	neutral	None	None	None	None	N
S/G	0.0867	likely_benign	0.0992	benign	-0.761	Destabilizing	0.027	N	0.536	neutral	D	0.710359801	None	None	N
S/H	0.2608	likely_benign	0.235	benign	-1.022	Destabilizing	0.38	N	0.603	neutral	None	None	None	None	N
S/I	0.1226	likely_benign	0.1352	benign	0.221	Stabilizing	0.317	N	0.595	neutral	N	0.517427367	None	None	N
S/K	0.6319	likely_pathogenic	0.5392	ambiguous	-0.211	Destabilizing	0.035	N	0.532	neutral	None	None	None	None	N
S/L	0.1076	likely_benign	0.1243	benign	0.221	Stabilizing	0.081	N	0.573	neutral	None	None	None	None	N
S/M	0.166	likely_benign	0.1748	benign	0.081	Stabilizing	0.791	D	0.595	neutral	None	None	None	None	N
S/N	0.1075	likely_benign	0.1139	benign	-0.451	Destabilizing	None	N	0.191	neutral	D	0.558853695	None	None	N
S/P	0.8925	likely_pathogenic	0.9166	pathogenic	0.026	Stabilizing	0.555	D	0.597	neutral	None	None	None	None	N
S/Q	0.4031	ambiguous	0.3698	ambiguous	-0.387	Destabilizing	0.38	N	0.58	neutral	None	None	None	None	N
S/R	0.5159	ambiguous	0.404	ambiguous	-0.265	Destabilizing	None	N	0.397	neutral	N	0.510488151	None	None	N
S/T	0.0696	likely_benign	0.0717	benign	-0.37	Destabilizing	0.001	N	0.191	neutral	N	0.442204551	None	None	N
S/V	0.1442	likely_benign	0.1598	benign	0.026	Stabilizing	0.081	N	0.567	neutral	None	None	None	None	N
S/W	0.3717	ambiguous	0.3815	ambiguous	-0.737	Destabilizing	0.935	D	0.671	neutral	None	None	None	None	N
S/Y	0.1873	likely_benign	0.1989	benign	-0.342	Destabilizing	0.791	D	0.601	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.