TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8622	26089;26090;26091	chr2:178715550;178715549;178715548	chr2:179580277;179580276;179580275
N2AB	8305	25138;25139;25140	chr2:178715550;178715549;178715548	chr2:179580277;179580276;179580275
N2A	7378	22357;22358;22359	chr2:178715550;178715549;178715548	chr2:179580277;179580276;179580275
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-71
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0831
• 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/Y	None	None	1.0	D	0.905	0.639	0.818437442364	gnomAD-4.0.0	1.59168E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	2.85932E-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	0.921	likely_pathogenic	0.9143	pathogenic	-1.578	Destabilizing	0.998	D	0.718	prob.delet.	None	None	disulfide	None	N
C/D	0.9998	likely_pathogenic	0.9997	pathogenic	-1.145	Destabilizing	1.0	D	0.891	deleterious	None	None	disulfide	None	N
C/E	0.9998	likely_pathogenic	0.9997	pathogenic	-0.902	Destabilizing	1.0	D	0.905	deleterious	None	None	disulfide	None	N
C/F	0.924	likely_pathogenic	0.8844	pathogenic	-1.025	Destabilizing	1.0	D	0.893	deleterious	D	0.55412965	disulfide	None	N
C/G	0.9246	likely_pathogenic	0.9081	pathogenic	-1.947	Destabilizing	1.0	D	0.876	deleterious	D	0.567006892	disulfide	None	N
C/H	0.999	likely_pathogenic	0.9984	pathogenic	-2.159	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	disulfide	None	N
C/I	0.9237	likely_pathogenic	0.8884	pathogenic	-0.579	Destabilizing	1.0	D	0.807	deleterious	None	None	disulfide	None	N
C/K	0.9998	likely_pathogenic	0.9997	pathogenic	-0.659	Destabilizing	1.0	D	0.889	deleterious	None	None	disulfide	None	N
C/L	0.8812	likely_pathogenic	0.8228	pathogenic	-0.579	Destabilizing	1.0	D	0.767	deleterious	None	None	disulfide	None	N
C/M	0.9666	likely_pathogenic	0.9534	pathogenic	0.156	Stabilizing	1.0	D	0.835	deleterious	None	None	disulfide	None	N
C/N	0.999	likely_pathogenic	0.9985	pathogenic	-1.285	Destabilizing	1.0	D	0.905	deleterious	None	None	disulfide	None	N
C/P	0.9996	likely_pathogenic	0.9994	pathogenic	-0.889	Destabilizing	1.0	D	0.905	deleterious	None	None	disulfide	None	N
C/Q	0.9993	likely_pathogenic	0.999	pathogenic	-0.805	Destabilizing	1.0	D	0.913	deleterious	None	None	disulfide	None	N
C/R	0.9968	likely_pathogenic	0.9951	pathogenic	-1.19	Destabilizing	1.0	D	0.91	deleterious	D	0.567006892	disulfide	None	N
C/S	0.9788	likely_pathogenic	0.9754	pathogenic	-1.606	Destabilizing	1.0	D	0.799	deleterious	D	0.567006892	disulfide	None	N
C/T	0.9841	likely_pathogenic	0.981	pathogenic	-1.162	Destabilizing	1.0	D	0.807	deleterious	None	None	disulfide	None	N
C/V	0.8172	likely_pathogenic	0.7845	pathogenic	-0.889	Destabilizing	1.0	D	0.786	deleterious	None	None	disulfide	None	N
C/W	0.9934	likely_pathogenic	0.9893	pathogenic	-1.362	Destabilizing	1.0	D	0.87	deleterious	D	0.567006892	disulfide	None	N
C/Y	0.9896	likely_pathogenic	0.9809	pathogenic	-1.149	Destabilizing	1.0	D	0.905	deleterious	D	0.567006892	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.