TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6833	20722;20723;20724	chr2:178725825;178725824;178725823	chr2:179590552;179590551;179590550
N2AB	6516	19771;19772;19773	chr2:178725825;178725824;178725823	chr2:179590552;179590551;179590550
N2A	5589	16990;16991;16992	chr2:178725825;178725824;178725823	chr2:179590552;179590551;179590550
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-52
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0614
• Site annotation: disulfide
• 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
C/R	None	None	0.975	D	0.743	0.853	0.896977869265	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
C/Y	rs2079243325	None	1.0	D	0.861	0.684	0.912907702155	gnomAD-3.1.2	6.57E-06	None	None	disulfide	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
C/Y	rs2079243325	None	1.0	D	0.861	0.684	0.912907702155	gnomAD-4.0.0	6.57237E-06	None	None	disulfide	None	N	None	0	6.55394E-05	None	0	0	None	0	0	0	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
C/A	0.9214	likely_pathogenic	0.9353	pathogenic	-1.5	Destabilizing	0.964	D	0.675	neutral	None	None	disulfide	None	N
C/D	0.9998	likely_pathogenic	0.9998	pathogenic	-1.705	Destabilizing	1.0	D	0.868	deleterious	None	None	disulfide	None	N
C/E	0.9997	likely_pathogenic	0.9998	pathogenic	-1.457	Destabilizing	1.0	D	0.861	deleterious	None	None	disulfide	None	N
C/F	0.8478	likely_pathogenic	0.9019	pathogenic	-0.874	Destabilizing	1.0	D	0.855	deleterious	D	0.67585762	disulfide	None	N
C/G	0.8535	likely_pathogenic	0.8878	pathogenic	-1.856	Destabilizing	0.996	D	0.855	deleterious	D	0.677068445	disulfide	None	N
C/H	0.9976	likely_pathogenic	0.9987	pathogenic	-2.062	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	disulfide	None	N
C/I	0.8493	likely_pathogenic	0.9056	pathogenic	-0.524	Destabilizing	1.0	D	0.759	deleterious	None	None	disulfide	None	N
C/K	0.9996	likely_pathogenic	0.9998	pathogenic	-1.131	Destabilizing	1.0	D	0.849	deleterious	None	None	disulfide	None	N
C/L	0.8041	likely_pathogenic	0.8564	pathogenic	-0.524	Destabilizing	0.996	D	0.75	deleterious	None	None	disulfide	None	N
C/M	0.9549	likely_pathogenic	0.9706	pathogenic	0.28	Stabilizing	1.0	D	0.753	deleterious	None	None	disulfide	None	N
C/N	0.9981	likely_pathogenic	0.9986	pathogenic	-1.85	Destabilizing	1.0	D	0.869	deleterious	None	None	disulfide	None	N
C/P	0.999	likely_pathogenic	0.9995	pathogenic	-0.829	Destabilizing	1.0	D	0.869	deleterious	None	None	disulfide	None	N
C/Q	0.9982	likely_pathogenic	0.999	pathogenic	-1.325	Destabilizing	1.0	D	0.869	deleterious	None	None	disulfide	None	N
C/R	0.9943	likely_pathogenic	0.997	pathogenic	-1.596	Destabilizing	0.975	D	0.743	deleterious	D	0.677068445	disulfide	None	N
C/S	0.9711	likely_pathogenic	0.9774	pathogenic	-2.091	Highly Destabilizing	0.999	D	0.761	deleterious	D	0.677068445	disulfide	None	N
C/T	0.9816	likely_pathogenic	0.986	pathogenic	-1.668	Destabilizing	0.999	D	0.778	deleterious	None	None	disulfide	None	N
C/V	0.7745	likely_pathogenic	0.8298	pathogenic	-0.829	Destabilizing	0.998	D	0.777	deleterious	None	None	disulfide	None	N
C/W	0.9897	likely_pathogenic	0.9945	pathogenic	-1.347	Destabilizing	1.0	D	0.843	deleterious	D	0.677068445	disulfide	None	N
C/Y	0.9778	likely_pathogenic	0.9871	pathogenic	-1.125	Destabilizing	1.0	D	0.861	deleterious	D	0.676866641	disulfide	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.