TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16739	50440;50441;50442	chr2:178612310;178612309;178612308	chr2:179477037;179477036;179477035
N2AB	15098	45517;45518;45519	chr2:178612310;178612309;178612308	chr2:179477037;179477036;179477035
N2A	14171	42736;42737;42738	chr2:178612310;178612309;178612308	chr2:179477037;179477036;179477035
N2B	7674	23245;23246;23247	chr2:178612310;178612309;178612308	chr2:179477037;179477036;179477035
Novex-1	7799	23620;23621;23622	chr2:178612310;178612309;178612308	chr2:179477037;179477036;179477035
Novex-2	7866	23821;23822;23823	chr2:178612310;178612309;178612308	chr2:179477037;179477036;179477035
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-9
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.1357
• 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
I/V	rs1553698265	None	None	N	0.212	0.064	0.21737058555	gnomAD-4.0.0	1.59395E-06	None	None	None	None	N	None	5.67472E-05	0	None	0	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
I/A	0.3765	ambiguous	0.3898	ambiguous	-2.035	Highly Destabilizing	0.016	N	0.648	neutral	None	None	None	None	N
I/C	0.8094	likely_pathogenic	0.8034	pathogenic	-1.3	Destabilizing	0.685	D	0.657	prob.neutral	None	None	None	None	N
I/D	0.9196	likely_pathogenic	0.9515	pathogenic	-1.807	Destabilizing	0.366	N	0.796	deleterious	None	None	None	None	N
I/E	0.8412	likely_pathogenic	0.891	pathogenic	-1.686	Destabilizing	0.366	N	0.791	deleterious	None	None	None	None	N
I/F	0.4623	ambiguous	0.5065	ambiguous	-1.18	Destabilizing	0.177	N	0.715	prob.delet.	N	0.473014083	None	None	N
I/G	0.7781	likely_pathogenic	0.8066	pathogenic	-2.482	Highly Destabilizing	0.366	N	0.781	deleterious	None	None	None	None	N
I/H	0.8939	likely_pathogenic	0.9219	pathogenic	-1.784	Destabilizing	0.869	D	0.767	deleterious	None	None	None	None	N
I/K	0.7715	likely_pathogenic	0.8614	pathogenic	-1.566	Destabilizing	0.366	N	0.784	deleterious	None	None	None	None	N
I/L	0.1237	likely_benign	0.1392	benign	-0.808	Destabilizing	None	N	0.209	neutral	N	0.415418346	None	None	N
I/M	0.1206	likely_benign	0.1398	benign	-0.703	Destabilizing	0.177	N	0.691	prob.delet.	N	0.474131129	None	None	N
I/N	0.5708	likely_pathogenic	0.6561	pathogenic	-1.61	Destabilizing	0.57	D	0.796	deleterious	N	0.474777637	None	None	N
I/P	0.9288	likely_pathogenic	0.9357	pathogenic	-1.19	Destabilizing	0.637	D	0.792	deleterious	None	None	None	None	N
I/Q	0.7713	likely_pathogenic	0.8372	pathogenic	-1.625	Destabilizing	0.637	D	0.775	deleterious	None	None	None	None	N
I/R	0.7274	likely_pathogenic	0.8312	pathogenic	-1.12	Destabilizing	0.366	N	0.792	deleterious	None	None	None	None	N
I/S	0.4774	ambiguous	0.5256	ambiguous	-2.281	Highly Destabilizing	0.058	N	0.715	prob.delet.	N	0.463282917	None	None	N
I/T	0.1531	likely_benign	0.169	benign	-2.031	Highly Destabilizing	0.03	N	0.721	deleterious	N	0.430885089	None	None	N
I/V	0.0797	likely_benign	0.0665	benign	-1.19	Destabilizing	None	N	0.212	neutral	N	0.453370261	None	None	N
I/W	0.9442	likely_pathogenic	0.9669	pathogenic	-1.426	Destabilizing	0.869	D	0.781	deleterious	None	None	None	None	N
I/Y	0.8733	likely_pathogenic	0.9073	pathogenic	-1.152	Destabilizing	0.366	N	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.