TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20432	61519;61520;61521	chr2:178590431;178590430;178590429	chr2:179455158;179455157;179455156
N2AB	18791	56596;56597;56598	chr2:178590431;178590430;178590429	chr2:179455158;179455157;179455156
N2A	17864	53815;53816;53817	chr2:178590431;178590430;178590429	chr2:179455158;179455157;179455156
N2B	11367	34324;34325;34326	chr2:178590431;178590430;178590429	chr2:179455158;179455157;179455156
Novex-1	11492	34699;34700;34701	chr2:178590431;178590430;178590429	chr2:179455158;179455157;179455156
Novex-2	11559	34900;34901;34902	chr2:178590431;178590430;178590429	chr2:179455158;179455157;179455156
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-36
• Domain position: 62
• Structural Position: 91
• Q(SASA): 0.1954
• 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
F/S	None	None	0.782	N	0.58	0.377	0.66614110018	gnomAD-4.0.0	3.18971E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.87985E-05	0
F/V	rs1287181968	-1.719	0.505	N	0.457	0.386	0.586295999888	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
F/V	rs1287181968	-1.719	0.505	N	0.457	0.386	0.586295999888	gnomAD-4.0.0	1.59484E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86302E-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
F/A	0.9671	likely_pathogenic	0.9471	pathogenic	-2.402	Highly Destabilizing	0.575	D	0.536	neutral	None	None	None	None	N
F/C	0.691	likely_pathogenic	0.6614	pathogenic	-1.819	Destabilizing	0.988	D	0.688	prob.neutral	N	0.468380842	None	None	N
F/D	0.9951	likely_pathogenic	0.9927	pathogenic	-2.428	Highly Destabilizing	0.906	D	0.692	prob.neutral	None	None	None	None	N
F/E	0.9941	likely_pathogenic	0.9901	pathogenic	-2.262	Highly Destabilizing	0.906	D	0.67	neutral	None	None	None	None	N
F/G	0.9862	likely_pathogenic	0.9771	pathogenic	-2.775	Highly Destabilizing	0.906	D	0.637	neutral	None	None	None	None	N
F/H	0.8657	likely_pathogenic	0.8531	pathogenic	-1.174	Destabilizing	0.826	D	0.565	neutral	None	None	None	None	N
F/I	0.8111	likely_pathogenic	0.7444	pathogenic	-1.215	Destabilizing	0.505	D	0.405	neutral	N	0.501895983	None	None	N
F/K	0.9894	likely_pathogenic	0.9836	pathogenic	-2.18	Highly Destabilizing	0.826	D	0.674	neutral	None	None	None	None	N
F/L	0.9672	likely_pathogenic	0.9593	pathogenic	-1.215	Destabilizing	0.174	N	0.445	neutral	N	0.480576562	None	None	N
F/M	0.8913	likely_pathogenic	0.8614	pathogenic	-1.01	Destabilizing	0.967	D	0.445	neutral	None	None	None	None	N
F/N	0.979	likely_pathogenic	0.9714	pathogenic	-2.623	Highly Destabilizing	0.906	D	0.71	prob.delet.	None	None	None	None	N
F/P	0.9996	likely_pathogenic	0.9994	pathogenic	-1.615	Destabilizing	0.967	D	0.747	deleterious	None	None	None	None	N
F/Q	0.9796	likely_pathogenic	0.9705	pathogenic	-2.555	Highly Destabilizing	0.906	D	0.738	prob.delet.	None	None	None	None	N
F/R	0.9737	likely_pathogenic	0.963	pathogenic	-1.688	Destabilizing	0.906	D	0.725	prob.delet.	None	None	None	None	N
F/S	0.9533	likely_pathogenic	0.9331	pathogenic	-3.238	Highly Destabilizing	0.782	D	0.58	neutral	N	0.473396701	None	None	N
F/T	0.9747	likely_pathogenic	0.9615	pathogenic	-2.962	Highly Destabilizing	0.906	D	0.579	neutral	None	None	None	None	N
F/V	0.7717	likely_pathogenic	0.7023	pathogenic	-1.615	Destabilizing	0.505	D	0.457	neutral	N	0.496735306	None	None	N
F/W	0.6344	likely_pathogenic	0.6304	pathogenic	-0.422	Destabilizing	0.906	D	0.461	neutral	None	None	None	None	N
F/Y	0.1743	likely_benign	0.1902	benign	-0.74	Destabilizing	None	N	0.178	neutral	N	0.394360299	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.