TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6591	19996;19997;19998	chr2:178727807;178727806;178727805	chr2:179592534;179592533;179592532
N2AB	6274	19045;19046;19047	chr2:178727807;178727806;178727805	chr2:179592534;179592533;179592532
N2A	5347	16264;16265;16266	chr2:178727807;178727806;178727805	chr2:179592534;179592533;179592532
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-50
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1173
• 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
V/G	rs2079619288	None	0.997	N	0.757	0.487	0.795264024752	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
V/G	rs2079619288	None	0.997	N	0.757	0.487	0.795264024752	gnomAD-4.0.0	2.56654E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.69092E-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
V/A	0.2354	likely_benign	0.2656	benign	-1.714	Destabilizing	0.543	D	0.267	neutral	N	0.493054708	None	None	N
V/C	0.8986	likely_pathogenic	0.9292	pathogenic	-1.282	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/D	0.9292	likely_pathogenic	0.9605	pathogenic	-1.368	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
V/E	0.7975	likely_pathogenic	0.8678	pathogenic	-1.247	Destabilizing	0.998	D	0.796	deleterious	D	0.524015119	None	None	N
V/F	0.508	ambiguous	0.5815	pathogenic	-1.027	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
V/G	0.5815	likely_pathogenic	0.635	pathogenic	-2.167	Highly Destabilizing	0.997	D	0.757	deleterious	N	0.512658814	None	None	N
V/H	0.9512	likely_pathogenic	0.9722	pathogenic	-1.635	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/I	0.0962	likely_benign	0.1057	benign	-0.514	Destabilizing	0.99	D	0.505	neutral	None	None	None	None	N
V/K	0.8541	likely_pathogenic	0.9075	pathogenic	-1.401	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/L	0.3848	ambiguous	0.4725	ambiguous	-0.514	Destabilizing	0.973	D	0.541	neutral	N	0.453427616	None	None	N
V/M	0.2516	likely_benign	0.299	benign	-0.51	Destabilizing	0.999	D	0.723	prob.delet.	N	0.501049019	None	None	N
V/N	0.8669	likely_pathogenic	0.9173	pathogenic	-1.403	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/P	0.9553	likely_pathogenic	0.9711	pathogenic	-0.881	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
V/Q	0.8126	likely_pathogenic	0.8744	pathogenic	-1.373	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/R	0.8081	likely_pathogenic	0.8773	pathogenic	-1.086	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/S	0.5915	likely_pathogenic	0.657	pathogenic	-2.093	Highly Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	N
V/T	0.3168	likely_benign	0.3629	ambiguous	-1.825	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	N
V/W	0.9706	likely_pathogenic	0.9831	pathogenic	-1.31	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/Y	0.9136	likely_pathogenic	0.9464	pathogenic	-0.978	Destabilizing	1.0	D	0.811	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.