TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4767	14524;14525;14526	chr2:178738154;178738153;178738152	chr2:179602881;179602880;179602879
N2AB	4450	13573;13574;13575	chr2:178738154;178738153;178738152	chr2:179602881;179602880;179602879
N2A	3523	10792;10793;10794	chr2:178738154;178738153;178738152	chr2:179602881;179602880;179602879
N2B	4404	13435;13436;13437	chr2:178738154;178738153;178738152	chr2:179602881;179602880;179602879
Novex-1	4529	13810;13811;13812	chr2:178738154;178738153;178738152	chr2:179602881;179602880;179602879
Novex-2	4596	14011;14012;14013	chr2:178738154;178738153;178738152	chr2:179602881;179602880;179602879
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-30
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.3695
• Predicted PPI site: I

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
C/Y	rs1175326019	None	0.996	N	0.591	0.348	0.775817181622	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
C/A	0.4071	ambiguous	0.4067	ambiguous	-1.281	Destabilizing	0.079	N	0.095	neutral	None	None	None	None	I
C/D	0.7909	likely_pathogenic	0.841	pathogenic	0.406	Stabilizing	0.939	D	0.605	neutral	None	None	None	None	I
C/E	0.8332	likely_pathogenic	0.828	pathogenic	0.451	Stabilizing	0.939	D	0.603	neutral	None	None	None	None	I
C/F	0.4846	ambiguous	0.5018	ambiguous	-0.912	Destabilizing	0.996	D	0.597	neutral	N	0.477807057	None	None	I
C/G	0.2267	likely_benign	0.2564	benign	-1.528	Destabilizing	0.826	D	0.48	neutral	N	0.42288028	None	None	I
C/H	0.71	likely_pathogenic	0.7117	pathogenic	-1.609	Destabilizing	0.999	D	0.567	neutral	None	None	None	None	I
C/I	0.7203	likely_pathogenic	0.7113	pathogenic	-0.685	Destabilizing	0.969	D	0.582	neutral	None	None	None	None	I
C/K	0.8631	likely_pathogenic	0.8593	pathogenic	-0.322	Destabilizing	0.939	D	0.577	neutral	None	None	None	None	I
C/L	0.6886	likely_pathogenic	0.7031	pathogenic	-0.685	Destabilizing	0.863	D	0.506	neutral	None	None	None	None	I
C/M	0.7425	likely_pathogenic	0.737	pathogenic	-0.128	Destabilizing	0.997	D	0.581	neutral	None	None	None	None	I
C/N	0.5987	likely_pathogenic	0.6523	pathogenic	-0.136	Destabilizing	0.939	D	0.601	neutral	None	None	None	None	I
C/P	0.9877	likely_pathogenic	0.9899	pathogenic	-0.857	Destabilizing	0.991	D	0.616	neutral	None	None	None	None	I
C/Q	0.6946	likely_pathogenic	0.6837	pathogenic	-0.145	Destabilizing	0.991	D	0.617	neutral	None	None	None	None	I
C/R	0.5383	ambiguous	0.519	ambiguous	-0.204	Destabilizing	0.988	D	0.616	neutral	N	0.42698487	None	None	I
C/S	0.2566	likely_benign	0.2779	benign	-0.703	Destabilizing	0.159	N	0.19	neutral	N	0.287130502	None	None	I
C/T	0.4257	ambiguous	0.4654	ambiguous	-0.486	Destabilizing	0.759	D	0.506	neutral	None	None	None	None	I
C/V	0.5922	likely_pathogenic	0.6182	pathogenic	-0.857	Destabilizing	0.939	D	0.591	neutral	None	None	None	None	I
C/W	0.7969	likely_pathogenic	0.8024	pathogenic	-0.854	Destabilizing	1.0	D	0.576	neutral	N	0.508640785	None	None	I
C/Y	0.6104	likely_pathogenic	0.6357	pathogenic	-0.792	Destabilizing	0.996	D	0.591	neutral	N	0.447357958	None	None	I

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.