TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32799	98620;98621;98622	chr2:178539670;178539669;178539668	chr2:179404397;179404396;179404395
N2AB	31158	93697;93698;93699	chr2:178539670;178539669;178539668	chr2:179404397;179404396;179404395
N2A	30231	90916;90917;90918	chr2:178539670;178539669;178539668	chr2:179404397;179404396;179404395
N2B	23734	71425;71426;71427	chr2:178539670;178539669;178539668	chr2:179404397;179404396;179404395
Novex-1	23859	71800;71801;71802	chr2:178539670;178539669;178539668	chr2:179404397;179404396;179404395
Novex-2	23926	72001;72002;72003	chr2:178539670;178539669;178539668	chr2:179404397;179404396;179404395
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-127
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2433
• 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
P/L	None	None	0.988	D	0.802	0.524	0.82415279977	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	2.28645E-05	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
P/A	0.5746	likely_pathogenic	0.4799	ambiguous	-2.155	Highly Destabilizing	0.919	D	0.555	neutral	D	0.529785922	None	None	N
P/C	0.8361	likely_pathogenic	0.7987	pathogenic	-2.274	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/D	0.9978	likely_pathogenic	0.9966	pathogenic	-3.431	Highly Destabilizing	0.991	D	0.743	deleterious	None	None	None	None	N
P/E	0.9921	likely_pathogenic	0.9886	pathogenic	-3.214	Highly Destabilizing	0.991	D	0.749	deleterious	None	None	None	None	N
P/F	0.9935	likely_pathogenic	0.9906	pathogenic	-1.139	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
P/G	0.975	likely_pathogenic	0.9617	pathogenic	-2.645	Highly Destabilizing	0.938	D	0.681	prob.neutral	None	None	None	None	N
P/H	0.9916	likely_pathogenic	0.9864	pathogenic	-2.332	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/I	0.7517	likely_pathogenic	0.7441	pathogenic	-0.777	Destabilizing	0.995	D	0.837	deleterious	None	None	None	None	N
P/K	0.9946	likely_pathogenic	0.9928	pathogenic	-1.784	Destabilizing	0.991	D	0.733	prob.delet.	None	None	None	None	N
P/L	0.7175	likely_pathogenic	0.6708	pathogenic	-0.777	Destabilizing	0.988	D	0.802	deleterious	D	0.565994432	None	None	N
P/M	0.924	likely_pathogenic	0.9059	pathogenic	-1.271	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/N	0.9951	likely_pathogenic	0.9926	pathogenic	-2.283	Highly Destabilizing	0.991	D	0.78	deleterious	None	None	None	None	N
P/Q	0.9824	likely_pathogenic	0.9736	pathogenic	-2.115	Highly Destabilizing	0.988	D	0.805	deleterious	D	0.555234011	None	None	N
P/R	0.9828	likely_pathogenic	0.9772	pathogenic	-1.636	Destabilizing	0.988	D	0.809	deleterious	D	0.548650645	None	None	N
P/S	0.945	likely_pathogenic	0.9138	pathogenic	-2.759	Highly Destabilizing	0.414	N	0.311	neutral	D	0.543624216	None	None	N
P/T	0.7806	likely_pathogenic	0.723	pathogenic	-2.411	Highly Destabilizing	0.976	D	0.744	deleterious	D	0.554980521	None	None	N
P/V	0.5447	ambiguous	0.5252	ambiguous	-1.214	Destabilizing	0.991	D	0.768	deleterious	None	None	None	None	N
P/W	0.999	likely_pathogenic	0.9985	pathogenic	-1.679	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/Y	0.9978	likely_pathogenic	0.9965	pathogenic	-1.375	Destabilizing	1.0	D	0.849	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.