TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16268	49027;49028;49029	chr2:178614712;178614711;178614710	chr2:179479439;179479438;179479437
N2AB	14627	44104;44105;44106	chr2:178614712;178614711;178614710	chr2:179479439;179479438;179479437
N2A	13700	41323;41324;41325	chr2:178614712;178614711;178614710	chr2:179479439;179479438;179479437
N2B	7203	21832;21833;21834	chr2:178614712;178614711;178614710	chr2:179479439;179479438;179479437
Novex-1	7328	22207;22208;22209	chr2:178614712;178614711;178614710	chr2:179479439;179479438;179479437
Novex-2	7395	22408;22409;22410	chr2:178614712;178614711;178614710	chr2:179479439;179479438;179479437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-110
• Domain position: 7
• Structural Position: 13
• Q(SASA): 0.1675
• 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
L/I	rs1474027032	None	0.004	N	0.266	0.074	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
L/I	rs1474027032	None	0.004	N	0.266	0.074	None	gnomAD-4.0.0	5.83361E-05	None	None	None	None	N	None	1.33826E-05	0	None	0	0	None	0	0	7.71986E-05	0	3.20914E-05

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
L/A	0.8009	likely_pathogenic	0.8204	pathogenic	-1.67	Destabilizing	0.648	D	0.607	neutral	None	None	None	None	N
L/C	0.8151	likely_pathogenic	0.807	pathogenic	-1.28	Destabilizing	0.993	D	0.737	prob.delet.	None	None	None	None	N
L/D	0.9861	likely_pathogenic	0.9879	pathogenic	-1.011	Destabilizing	0.929	D	0.835	deleterious	None	None	None	None	N
L/E	0.9078	likely_pathogenic	0.9121	pathogenic	-0.969	Destabilizing	0.929	D	0.844	deleterious	None	None	None	None	N
L/F	0.4543	ambiguous	0.4662	ambiguous	-1.054	Destabilizing	0.83	D	0.757	deleterious	D	0.566409796	None	None	N
L/G	0.974	likely_pathogenic	0.9771	pathogenic	-2.033	Highly Destabilizing	0.929	D	0.831	deleterious	None	None	None	None	N
L/H	0.8174	likely_pathogenic	0.8349	pathogenic	-1.204	Destabilizing	0.991	D	0.817	deleterious	D	0.556799195	None	None	N
L/I	0.0808	likely_benign	0.0854	benign	-0.734	Destabilizing	0.004	N	0.266	neutral	N	0.479930241	None	None	N
L/K	0.7606	likely_pathogenic	0.7777	pathogenic	-1.268	Destabilizing	0.929	D	0.825	deleterious	None	None	None	None	N
L/M	0.1628	likely_benign	0.179	benign	-0.733	Destabilizing	0.866	D	0.767	deleterious	None	None	None	None	N
L/N	0.8919	likely_pathogenic	0.9075	pathogenic	-1.185	Destabilizing	0.976	D	0.837	deleterious	None	None	None	None	N
L/P	0.9884	likely_pathogenic	0.9905	pathogenic	-1.015	Destabilizing	0.968	D	0.837	deleterious	D	0.604457417	None	None	N
L/Q	0.6763	likely_pathogenic	0.7054	pathogenic	-1.269	Destabilizing	0.993	D	0.828	deleterious	None	None	None	None	N
L/R	0.7894	likely_pathogenic	0.8081	pathogenic	-0.753	Destabilizing	0.908	D	0.843	deleterious	D	0.541353694	None	None	N
L/S	0.9234	likely_pathogenic	0.9359	pathogenic	-1.841	Destabilizing	0.929	D	0.826	deleterious	None	None	None	None	N
L/T	0.7558	likely_pathogenic	0.7857	pathogenic	-1.662	Destabilizing	0.866	D	0.767	deleterious	None	None	None	None	N
L/V	0.1456	likely_benign	0.1563	benign	-1.015	Destabilizing	0.09	N	0.467	neutral	N	0.492125213	None	None	N
L/W	0.8138	likely_pathogenic	0.8247	pathogenic	-1.13	Destabilizing	0.993	D	0.772	deleterious	None	None	None	None	N
L/Y	0.791	likely_pathogenic	0.8012	pathogenic	-0.911	Destabilizing	0.929	D	0.824	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.