TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21047	63364;63365;63366	chr2:178588586;178588585;178588584	chr2:179453313;179453312;179453311
N2AB	19406	58441;58442;58443	chr2:178588586;178588585;178588584	chr2:179453313;179453312;179453311
N2A	18479	55660;55661;55662	chr2:178588586;178588585;178588584	chr2:179453313;179453312;179453311
N2B	11982	36169;36170;36171	chr2:178588586;178588585;178588584	chr2:179453313;179453312;179453311
Novex-1	12107	36544;36545;36546	chr2:178588586;178588585;178588584	chr2:179453313;179453312;179453311
Novex-2	12174	36745;36746;36747	chr2:178588586;178588585;178588584	chr2:179453313;179453312;179453311
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-40
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1218
• 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
G/E	None	None	1.0	D	0.91	0.592	0.553955064939	gnomAD-4.0.0	1.75548E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.09853E-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
G/A	0.6448	likely_pathogenic	0.6733	pathogenic	-0.901	Destabilizing	1.0	D	0.704	prob.neutral	D	0.54084756	None	None	N
G/C	0.8725	likely_pathogenic	0.9024	pathogenic	-1.051	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/D	0.9822	likely_pathogenic	0.9818	pathogenic	-1.694	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/E	0.9887	likely_pathogenic	0.9885	pathogenic	-1.749	Destabilizing	1.0	D	0.91	deleterious	D	0.529998234	None	None	N
G/F	0.996	likely_pathogenic	0.9972	pathogenic	-1.13	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/H	0.9899	likely_pathogenic	0.991	pathogenic	-1.454	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/I	0.9931	likely_pathogenic	0.9946	pathogenic	-0.516	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/K	0.9971	likely_pathogenic	0.9968	pathogenic	-1.471	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
G/L	0.9882	likely_pathogenic	0.9907	pathogenic	-0.516	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
G/M	0.9912	likely_pathogenic	0.993	pathogenic	-0.44	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
G/N	0.9761	likely_pathogenic	0.9794	pathogenic	-1.15	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
G/P	0.9982	likely_pathogenic	0.9985	pathogenic	-0.605	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
G/Q	0.9881	likely_pathogenic	0.9882	pathogenic	-1.37	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
G/R	0.9888	likely_pathogenic	0.9887	pathogenic	-1.085	Destabilizing	1.0	D	0.911	deleterious	N	0.501044652	None	None	N
G/S	0.2509	likely_benign	0.2627	benign	-1.357	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
G/T	0.8441	likely_pathogenic	0.8669	pathogenic	-1.349	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
G/V	0.9846	likely_pathogenic	0.9875	pathogenic	-0.605	Destabilizing	1.0	D	0.902	deleterious	D	0.542115008	None	None	N
G/W	0.9857	likely_pathogenic	0.9887	pathogenic	-1.475	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/Y	0.9935	likely_pathogenic	0.9945	pathogenic	-1.105	Destabilizing	1.0	D	0.869	deleterious	None	None	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.