TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32938	99037;99038;99039	chr2:178539123;178539122;178539121	chr2:179403850;179403849;179403848
N2AB	31297	94114;94115;94116	chr2:178539123;178539122;178539121	chr2:179403850;179403849;179403848
N2A	30370	91333;91334;91335	chr2:178539123;178539122;178539121	chr2:179403850;179403849;179403848
N2B	23873	71842;71843;71844	chr2:178539123;178539122;178539121	chr2:179403850;179403849;179403848
Novex-1	23998	72217;72218;72219	chr2:178539123;178539122;178539121	chr2:179403850;179403849;179403848
Novex-2	24065	72418;72419;72420	chr2:178539123;178539122;178539121	chr2:179403850;179403849;179403848
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-128
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.459
• 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
E/Q	rs1170456580	-0.45	1.0	N	0.601	0.278	0.225215365344	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs1170456580	-0.45	1.0	N	0.601	0.278	0.225215365344	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
E/A	0.6451	likely_pathogenic	0.5406	ambiguous	-1.156	Destabilizing	0.999	D	0.64	neutral	N	0.50122398	None	None	N
E/C	0.9877	likely_pathogenic	0.9769	pathogenic	-0.496	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
E/D	0.5441	ambiguous	0.4832	ambiguous	-1.002	Destabilizing	0.999	D	0.421	neutral	N	0.471690506	None	None	N
E/F	0.988	likely_pathogenic	0.9777	pathogenic	-0.665	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/G	0.7213	likely_pathogenic	0.6493	pathogenic	-1.485	Destabilizing	1.0	D	0.655	neutral	D	0.523466121	None	None	N
E/H	0.9674	likely_pathogenic	0.9481	pathogenic	-0.763	Destabilizing	1.0	D	0.618	neutral	None	None	None	None	N
E/I	0.8907	likely_pathogenic	0.8285	pathogenic	-0.26	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.8239	likely_pathogenic	0.7588	pathogenic	-0.444	Destabilizing	0.999	D	0.575	neutral	N	0.467687409	None	None	N
E/L	0.8752	likely_pathogenic	0.7764	pathogenic	-0.26	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/M	0.8973	likely_pathogenic	0.8269	pathogenic	0.246	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
E/N	0.8515	likely_pathogenic	0.7992	pathogenic	-0.977	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/P	0.92	likely_pathogenic	0.9048	pathogenic	-0.539	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/Q	0.6253	likely_pathogenic	0.5119	ambiguous	-0.89	Destabilizing	1.0	D	0.601	neutral	N	0.500010471	None	None	N
E/R	0.9015	likely_pathogenic	0.8598	pathogenic	-0.153	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
E/S	0.8415	likely_pathogenic	0.7896	pathogenic	-1.268	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
E/T	0.8766	likely_pathogenic	0.8304	pathogenic	-0.985	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/V	0.7452	likely_pathogenic	0.6658	pathogenic	-0.539	Destabilizing	1.0	D	0.717	prob.delet.	N	0.469802303	None	None	N
E/W	0.9975	likely_pathogenic	0.9953	pathogenic	-0.325	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/Y	0.9786	likely_pathogenic	0.9593	pathogenic	-0.377	Destabilizing	1.0	D	0.675	prob.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.