TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33386	100381;100382;100383	chr2:178536953;178536952;178536951	chr2:179401680;179401679;179401678
N2AB	31745	95458;95459;95460	chr2:178536953;178536952;178536951	chr2:179401680;179401679;179401678
N2A	30818	92677;92678;92679	chr2:178536953;178536952;178536951	chr2:179401680;179401679;179401678
N2B	24321	73186;73187;73188	chr2:178536953;178536952;178536951	chr2:179401680;179401679;179401678
Novex-1	24446	73561;73562;73563	chr2:178536953;178536952;178536951	chr2:179401680;179401679;179401678
Novex-2	24513	73762;73763;73764	chr2:178536953;178536952;178536951	chr2:179401680;179401679;179401678
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: Fn3-130
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0572
• 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/T	None	None	0.799	N	0.724	0.294	0.569563978121	gnomAD-4.0.0	2.74622E-06	None	None	None	None	N	None	0	2.24709E-05	None	0	0	None	0	0	2.7071E-06	0	0
I/V	rs1691868838	None	0.022	N	0.165	0.08	0.518038692251	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1691868838	None	0.022	N	0.165	0.08	0.518038692251	gnomAD-4.0.0	1.24349E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7006E-06	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	0.8337	likely_pathogenic	0.868	pathogenic	-3.005	Highly Destabilizing	0.685	D	0.671	prob.neutral	None	None	None	None	N
I/C	0.9177	likely_pathogenic	0.9268	pathogenic	-2.482	Highly Destabilizing	0.998	D	0.703	prob.delet.	None	None	None	None	N
I/D	0.9972	likely_pathogenic	0.9978	pathogenic	-3.575	Highly Destabilizing	0.991	D	0.803	deleterious	None	None	None	None	N
I/E	0.9896	likely_pathogenic	0.9927	pathogenic	-3.336	Highly Destabilizing	0.974	D	0.761	deleterious	None	None	None	None	N
I/F	0.6096	likely_pathogenic	0.5808	pathogenic	-1.648	Destabilizing	0.933	D	0.695	prob.delet.	N	0.515859784	None	None	N
I/G	0.9794	likely_pathogenic	0.9829	pathogenic	-3.529	Highly Destabilizing	0.974	D	0.747	deleterious	None	None	None	None	N
I/H	0.9888	likely_pathogenic	0.9909	pathogenic	-2.828	Highly Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
I/K	0.9774	likely_pathogenic	0.9813	pathogenic	-2.275	Highly Destabilizing	0.949	D	0.761	deleterious	None	None	None	None	N
I/L	0.2907	likely_benign	0.2721	benign	-1.458	Destabilizing	0.11	N	0.475	neutral	N	0.478896119	None	None	N
I/M	0.2646	likely_benign	0.2471	benign	-1.684	Destabilizing	0.451	N	0.511	neutral	N	0.499698253	None	None	N
I/N	0.9507	likely_pathogenic	0.9597	pathogenic	-2.723	Highly Destabilizing	0.989	D	0.791	deleterious	N	0.468260777	None	None	N
I/P	0.9363	likely_pathogenic	0.9521	pathogenic	-1.961	Destabilizing	0.991	D	0.798	deleterious	None	None	None	None	N
I/Q	0.9623	likely_pathogenic	0.9728	pathogenic	-2.559	Highly Destabilizing	0.974	D	0.79	deleterious	None	None	None	None	N
I/R	0.961	likely_pathogenic	0.9688	pathogenic	-1.961	Destabilizing	0.974	D	0.788	deleterious	None	None	None	None	N
I/S	0.9009	likely_pathogenic	0.925	pathogenic	-3.357	Highly Destabilizing	0.966	D	0.713	prob.delet.	N	0.463145442	None	None	N
I/T	0.8858	likely_pathogenic	0.8965	pathogenic	-2.984	Highly Destabilizing	0.799	D	0.724	deleterious	N	0.451405661	None	None	N
I/V	0.1939	likely_benign	0.19	benign	-1.961	Destabilizing	0.022	N	0.165	neutral	N	0.473050369	None	None	N
I/W	0.984	likely_pathogenic	0.9848	pathogenic	-2.01	Highly Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
I/Y	0.9626	likely_pathogenic	0.9667	pathogenic	-1.868	Destabilizing	0.974	D	0.745	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.