TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8809	26650;26651;26652	chr2:178714349;178714348;178714347	chr2:179579076;179579075;179579074
N2AB	8492	25699;25700;25701	chr2:178714349;178714348;178714347	chr2:179579076;179579075;179579074
N2A	7565	22918;22919;22920	chr2:178714349;178714348;178714347	chr2:179579076;179579075;179579074
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: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-73
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0638
• 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	rs753253530	-1.014	1.0	D	0.901	0.768	0.816451128208	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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	0.6428	likely_pathogenic	0.7522	pathogenic	-1.325	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
C/D	0.9973	likely_pathogenic	0.9991	pathogenic	-1.509	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
C/E	0.998	likely_pathogenic	0.9993	pathogenic	-1.248	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
C/F	0.6015	likely_pathogenic	0.7422	pathogenic	-0.735	Destabilizing	1.0	D	0.888	deleterious	D	0.533885801	None	None	N
C/G	0.5108	ambiguous	0.6742	pathogenic	-1.686	Destabilizing	1.0	D	0.869	deleterious	D	0.558283933	None	None	N
C/H	0.9853	likely_pathogenic	0.9944	pathogenic	-1.906	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
C/I	0.6374	likely_pathogenic	0.7366	pathogenic	-0.34	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
C/K	0.9982	likely_pathogenic	0.9994	pathogenic	-0.788	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
C/L	0.6116	likely_pathogenic	0.7089	pathogenic	-0.34	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
C/M	0.8655	likely_pathogenic	0.9122	pathogenic	0.094	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
C/N	0.9791	likely_pathogenic	0.9922	pathogenic	-1.531	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
C/P	0.9949	likely_pathogenic	0.9975	pathogenic	-0.647	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
C/Q	0.9913	likely_pathogenic	0.9965	pathogenic	-0.98	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
C/R	0.9787	likely_pathogenic	0.9915	pathogenic	-1.363	Destabilizing	1.0	D	0.901	deleterious	D	0.558283933	None	None	N
C/S	0.7224	likely_pathogenic	0.855	pathogenic	-1.755	Destabilizing	1.0	D	0.806	deleterious	D	0.558283933	None	None	N
C/T	0.8421	likely_pathogenic	0.9075	pathogenic	-1.312	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
C/V	0.5124	ambiguous	0.5883	pathogenic	-0.647	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
C/W	0.9548	likely_pathogenic	0.9809	pathogenic	-1.213	Destabilizing	1.0	D	0.877	deleterious	D	0.558283933	None	None	N
C/Y	0.8789	likely_pathogenic	0.9453	pathogenic	-0.946	Destabilizing	1.0	D	0.901	deleterious	D	0.558283933	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.