TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5139	15640;15641;15642	chr2:178734409;178734408;178734407	chr2:179599136;179599135;179599134
N2AB	4822	14689;14690;14691	chr2:178734409;178734408;178734407	chr2:179599136;179599135;179599134
N2A	3895	11908;11909;11910	chr2:178734409;178734408;178734407	chr2:179599136;179599135;179599134
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-34
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.4984
• Predicted PPI site: I

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/G	rs876658040	None	0.999	N	0.423	0.538	0.394685799254	gnomAD-4.0.0	1.59162E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85884E-06	0	0
S/N	rs2081075120	None	0.999	N	0.496	0.343	0.352048277211	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/N	rs2081075120	None	0.999	N	0.496	0.343	0.352048277211	gnomAD-4.0.0	1.85922E-06	None	None	None	None	I	None	0	1.66717E-05	None	0	0	None	0	0	1.69532E-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
S/A	0.0794	likely_benign	0.0797	benign	-0.192	Destabilizing	0.998	D	0.411	neutral	None	None	None	None	I
S/C	0.2366	likely_benign	0.2085	benign	-0.354	Destabilizing	1.0	D	0.725	prob.delet.	D	0.654571897	None	None	I
S/D	0.6818	likely_pathogenic	0.5183	ambiguous	0.147	Stabilizing	0.999	D	0.53	neutral	None	None	None	None	I
S/E	0.7859	likely_pathogenic	0.6427	pathogenic	0.042	Stabilizing	0.999	D	0.517	neutral	None	None	None	None	I
S/F	0.29	likely_benign	0.2913	benign	-0.931	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
S/G	0.1055	likely_benign	0.0908	benign	-0.245	Destabilizing	0.999	D	0.423	neutral	N	0.516619085	None	None	I
S/H	0.5449	ambiguous	0.4015	ambiguous	-0.597	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
S/I	0.2171	likely_benign	0.1817	benign	-0.185	Destabilizing	1.0	D	0.743	deleterious	N	0.51957417	None	None	I
S/K	0.8694	likely_pathogenic	0.6634	pathogenic	-0.348	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	I
S/L	0.1164	likely_benign	0.124	benign	-0.185	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
S/M	0.2432	likely_benign	0.2333	benign	-0.147	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
S/N	0.2207	likely_benign	0.1522	benign	-0.137	Destabilizing	0.999	D	0.496	neutral	N	0.519291441	None	None	I
S/P	0.2066	likely_benign	0.184	benign	-0.162	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
S/Q	0.6907	likely_pathogenic	0.5267	ambiguous	-0.347	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
S/R	0.8271	likely_pathogenic	0.5518	ambiguous	-0.12	Destabilizing	1.0	D	0.692	prob.neutral	N	0.511623139	None	None	I
S/T	0.0881	likely_benign	0.0884	benign	-0.242	Destabilizing	0.999	D	0.395	neutral	N	0.493666226	None	None	I
S/V	0.2021	likely_benign	0.1841	benign	-0.162	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
S/W	0.5047	ambiguous	0.4645	ambiguous	-1.012	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
S/Y	0.2965	likely_benign	0.2741	benign	-0.689	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I

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.