TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32833	98722;98723;98724	chr2:178539568;178539567;178539566	chr2:179404295;179404294;179404293
N2AB	31192	93799;93800;93801	chr2:178539568;178539567;178539566	chr2:179404295;179404294;179404293
N2A	30265	91018;91019;91020	chr2:178539568;178539567;178539566	chr2:179404295;179404294;179404293
N2B	23768	71527;71528;71529	chr2:178539568;178539567;178539566	chr2:179404295;179404294;179404293
Novex-1	23893	71902;71903;71904	chr2:178539568;178539567;178539566	chr2:179404295;179404294;179404293
Novex-2	23960	72103;72104;72105	chr2:178539568;178539567;178539566	chr2:179404295;179404294;179404293
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-127
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0699
• 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/F	rs1368567004	-1.764	0.782	N	0.679	0.319	0.657373984822	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
L/F	rs1368567004	-1.764	0.782	N	0.679	0.319	0.657373984822	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88232E-05	0	0	0	0
L/P	None	None	0.957	N	0.876	0.66	0.855347383591	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	4.76644E-05	0	None	0	0	0	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	0.7984	likely_pathogenic	0.7277	pathogenic	-2.992	Highly Destabilizing	0.218	N	0.667	neutral	None	None	None	None	N
L/C	0.843	likely_pathogenic	0.8044	pathogenic	-2.089	Highly Destabilizing	0.973	D	0.794	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9978	pathogenic	-3.618	Highly Destabilizing	0.906	D	0.876	deleterious	None	None	None	None	N
L/E	0.9919	likely_pathogenic	0.9855	pathogenic	-3.276	Highly Destabilizing	0.906	D	0.869	deleterious	None	None	None	None	N
L/F	0.715	likely_pathogenic	0.6351	pathogenic	-1.733	Destabilizing	0.782	D	0.679	prob.neutral	N	0.500254049	None	None	N
L/G	0.9794	likely_pathogenic	0.9635	pathogenic	-3.622	Highly Destabilizing	0.906	D	0.856	deleterious	None	None	None	None	N
L/H	0.9871	likely_pathogenic	0.9773	pathogenic	-3.259	Highly Destabilizing	0.988	D	0.877	deleterious	N	0.500507539	None	None	N
L/I	0.0817	likely_benign	0.0738	benign	-1.078	Destabilizing	0.003	N	0.313	neutral	N	0.369192496	None	None	N
L/K	0.9909	likely_pathogenic	0.9857	pathogenic	-2.263	Highly Destabilizing	0.906	D	0.815	deleterious	None	None	None	None	N
L/M	0.3134	likely_benign	0.2747	benign	-1.284	Destabilizing	0.826	D	0.629	neutral	None	None	None	None	N
L/N	0.993	likely_pathogenic	0.9879	pathogenic	-3.035	Highly Destabilizing	0.967	D	0.887	deleterious	None	None	None	None	N
L/P	0.9855	likely_pathogenic	0.9733	pathogenic	-1.71	Destabilizing	0.957	D	0.876	deleterious	N	0.488986649	None	None	N
L/Q	0.976	likely_pathogenic	0.9608	pathogenic	-2.641	Highly Destabilizing	0.967	D	0.871	deleterious	None	None	None	None	N
L/R	0.9818	likely_pathogenic	0.9707	pathogenic	-2.353	Highly Destabilizing	0.879	D	0.859	deleterious	N	0.500507539	None	None	N
L/S	0.9741	likely_pathogenic	0.9548	pathogenic	-3.579	Highly Destabilizing	0.826	D	0.778	deleterious	None	None	None	None	N
L/T	0.8149	likely_pathogenic	0.7407	pathogenic	-3.066	Highly Destabilizing	0.575	D	0.661	neutral	None	None	None	None	N
L/V	0.0815	likely_benign	0.0627	benign	-1.71	Destabilizing	0.001	N	0.331	neutral	N	0.348619649	None	None	N
L/W	0.9674	likely_pathogenic	0.946	pathogenic	-2.082	Highly Destabilizing	0.991	D	0.837	deleterious	None	None	None	None	N
L/Y	0.9777	likely_pathogenic	0.9636	pathogenic	-1.942	Destabilizing	0.906	D	0.77	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.