TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7868	23827;23828;23829	chr2:178720040;178720039;178720038	chr2:179584767;179584766;179584765
N2AB	7551	22876;22877;22878	chr2:178720040;178720039;178720038	chr2:179584767;179584766;179584765
N2A	6624	20095;20096;20097	chr2:178720040;178720039;178720038	chr2:179584767;179584766;179584765
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-63
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0685
• 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	rs1158489320	None	1.0	D	0.906	0.696	0.818476300364	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
C/R	rs1158489320	None	1.0	D	0.906	0.696	0.818476300364	gnomAD-4.0.0	4.33878E-06	None	None	None	None	N	None	0	0	None	0	2.23025E-05	None	0	0	5.0863E-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
C/A	0.9472	likely_pathogenic	0.9299	pathogenic	-1.204	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
C/D	0.9999	likely_pathogenic	0.9999	pathogenic	-1.523	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
C/E	0.9999	likely_pathogenic	0.9999	pathogenic	-1.26	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
C/F	0.8715	likely_pathogenic	0.8607	pathogenic	-0.644	Destabilizing	1.0	D	0.89	deleterious	D	0.538823325	None	None	N
C/G	0.9063	likely_pathogenic	0.8823	pathogenic	-1.553	Destabilizing	1.0	D	0.874	deleterious	D	0.563056873	None	None	N
C/H	0.9991	likely_pathogenic	0.999	pathogenic	-1.801	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
C/I	0.8863	likely_pathogenic	0.8734	pathogenic	-0.251	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
C/K	0.9999	likely_pathogenic	0.9999	pathogenic	-0.726	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
C/L	0.7991	likely_pathogenic	0.7609	pathogenic	-0.251	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
C/M	0.9666	likely_pathogenic	0.9606	pathogenic	-0.044	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
C/N	0.999	likely_pathogenic	0.9987	pathogenic	-1.477	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
C/P	0.9995	likely_pathogenic	0.9993	pathogenic	-0.548	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
C/Q	0.9994	likely_pathogenic	0.9993	pathogenic	-0.909	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
C/R	0.9984	likely_pathogenic	0.9983	pathogenic	-1.352	Destabilizing	1.0	D	0.906	deleterious	D	0.563056873	None	None	N
C/S	0.9789	likely_pathogenic	0.9725	pathogenic	-1.667	Destabilizing	1.0	D	0.803	deleterious	D	0.563056873	None	None	N
C/T	0.9832	likely_pathogenic	0.9777	pathogenic	-1.231	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
C/V	0.8127	likely_pathogenic	0.7884	pathogenic	-0.548	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
C/W	0.9946	likely_pathogenic	0.9944	pathogenic	-1.157	Destabilizing	1.0	D	0.877	deleterious	D	0.563056873	None	None	N
C/Y	0.9865	likely_pathogenic	0.9843	pathogenic	-0.869	Destabilizing	1.0	D	0.903	deleterious	D	0.563056873	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.