TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31448	94567;94568;94569	chr2:178547183;178547182;178547181	chr2:179411910;179411909;179411908
N2AB	29807	89644;89645;89646	chr2:178547183;178547182;178547181	chr2:179411910;179411909;179411908
N2A	28880	86863;86864;86865	chr2:178547183;178547182;178547181	chr2:179411910;179411909;179411908
N2B	22383	67372;67373;67374	chr2:178547183;178547182;178547181	chr2:179411910;179411909;179411908
Novex-1	22508	67747;67748;67749	chr2:178547183;178547182;178547181	chr2:179411910;179411909;179411908
Novex-2	22575	67948;67949;67950	chr2:178547183;178547182;178547181	chr2:179411910;179411909;179411908
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-117
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.1706
• 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
K/N	rs1475927387	None	1.0	N	0.735	0.434	0.268211541103	gnomAD-4.0.0	1.36839E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79893E-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
K/A	0.9947	likely_pathogenic	0.9945	pathogenic	-1.458	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
K/C	0.9943	likely_pathogenic	0.9942	pathogenic	-1.529	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
K/D	0.9995	likely_pathogenic	0.9996	pathogenic	-1.897	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
K/E	0.9954	likely_pathogenic	0.9957	pathogenic	-1.613	Destabilizing	0.999	D	0.566	neutral	N	0.494664053	None	None	N
K/F	0.999	likely_pathogenic	0.9991	pathogenic	-0.649	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
K/G	0.9962	likely_pathogenic	0.9963	pathogenic	-1.921	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/H	0.9759	likely_pathogenic	0.9772	pathogenic	-2.052	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
K/I	0.9953	likely_pathogenic	0.9948	pathogenic	-0.15	Destabilizing	1.0	D	0.901	deleterious	N	0.501464909	None	None	N
K/L	0.9834	likely_pathogenic	0.9822	pathogenic	-0.15	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/M	0.9632	likely_pathogenic	0.9647	pathogenic	-0.568	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/N	0.9982	likely_pathogenic	0.9982	pathogenic	-1.812	Destabilizing	1.0	D	0.735	prob.delet.	N	0.48994402	None	None	N
K/P	0.9998	likely_pathogenic	0.9997	pathogenic	-0.566	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
K/Q	0.9532	likely_pathogenic	0.9512	pathogenic	-1.446	Destabilizing	1.0	D	0.712	prob.delet.	N	0.469785395	None	None	N
K/R	0.3338	likely_benign	0.3371	benign	-1.279	Destabilizing	0.999	D	0.531	neutral	N	0.44546391	None	None	N
K/S	0.9986	likely_pathogenic	0.9987	pathogenic	-2.295	Highly Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
K/T	0.9932	likely_pathogenic	0.9932	pathogenic	-1.77	Destabilizing	1.0	D	0.823	deleterious	N	0.49643848	None	None	N
K/V	0.9918	likely_pathogenic	0.9913	pathogenic	-0.566	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
K/W	0.9983	likely_pathogenic	0.9983	pathogenic	-0.783	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
K/Y	0.994	likely_pathogenic	0.9941	pathogenic	-0.421	Destabilizing	1.0	D	0.886	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.