TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6117	18574;18575;18576	chr2:178729904;178729903;178729902	chr2:179594631;179594630;179594629
N2AB	5800	17623;17624;17625	chr2:178729904;178729903;178729902	chr2:179594631;179594630;179594629
N2A	4873	14842;14843;14844	chr2:178729904;178729903;178729902	chr2:179594631;179594630;179594629
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-45
• Domain position: 13
• Structural Position: 16
• Q(SASA): 0.1856
• 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
L/M	rs2154307656	None	0.994	D	0.561	0.239	0.586633458331	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/P	None	None	0.998	D	0.653	0.624	0.863965248906	gnomAD-4.0.0	3.18489E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71886E-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
L/A	0.3804	ambiguous	0.4289	ambiguous	-2.143	Highly Destabilizing	0.931	D	0.528	neutral	None	None	None	None	N
L/C	0.652	likely_pathogenic	0.6605	pathogenic	-1.455	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	N
L/D	0.9052	likely_pathogenic	0.9125	pathogenic	-1.81	Destabilizing	0.996	D	0.652	neutral	None	None	None	None	N
L/E	0.5758	likely_pathogenic	0.5947	pathogenic	-1.745	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	N
L/F	0.1796	likely_benign	0.2015	benign	-1.418	Destabilizing	0.996	D	0.582	neutral	None	None	None	None	N
L/G	0.7004	likely_pathogenic	0.7379	pathogenic	-2.539	Highly Destabilizing	0.996	D	0.648	neutral	None	None	None	None	N
L/H	0.4158	ambiguous	0.4656	ambiguous	-1.774	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
L/I	0.1211	likely_benign	0.1213	benign	-1.081	Destabilizing	0.871	D	0.513	neutral	None	None	None	None	N
L/K	0.4522	ambiguous	0.4711	ambiguous	-1.523	Destabilizing	0.996	D	0.604	neutral	None	None	None	None	N
L/M	0.1366	likely_benign	0.1467	benign	-0.942	Destabilizing	0.994	D	0.561	neutral	D	0.533867621	None	None	N
L/N	0.7401	likely_pathogenic	0.7545	pathogenic	-1.433	Destabilizing	0.996	D	0.653	neutral	None	None	None	None	N
L/P	0.813	likely_pathogenic	0.8028	pathogenic	-1.408	Destabilizing	0.998	D	0.653	neutral	D	0.524421418	None	None	N
L/Q	0.244	likely_benign	0.2786	benign	-1.557	Destabilizing	0.998	D	0.602	neutral	N	0.507079175	None	None	N
L/R	0.3265	likely_benign	0.3598	ambiguous	-0.99	Destabilizing	0.994	D	0.613	neutral	N	0.506825686	None	None	N
L/S	0.4632	ambiguous	0.5009	ambiguous	-2.112	Highly Destabilizing	0.942	D	0.583	neutral	None	None	None	None	N
L/T	0.3684	ambiguous	0.3984	ambiguous	-1.927	Destabilizing	0.304	N	0.389	neutral	None	None	None	None	N
L/V	0.1057	likely_benign	0.1101	benign	-1.408	Destabilizing	0.122	N	0.204	neutral	N	0.384269097	None	None	N
L/W	0.3883	ambiguous	0.4277	ambiguous	-1.55	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
L/Y	0.5328	ambiguous	0.5684	pathogenic	-1.33	Destabilizing	0.999	D	0.599	neutral	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.