TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23350	70273;70274;70275	chr2:178576084;178576083;178576082	chr2:179440811;179440810;179440809
N2AB	21709	65350;65351;65352	chr2:178576084;178576083;178576082	chr2:179440811;179440810;179440809
N2A	20782	62569;62570;62571	chr2:178576084;178576083;178576082	chr2:179440811;179440810;179440809
N2B	14285	43078;43079;43080	chr2:178576084;178576083;178576082	chr2:179440811;179440810;179440809
Novex-1	14410	43453;43454;43455	chr2:178576084;178576083;178576082	chr2:179440811;179440810;179440809
Novex-2	14477	43654;43655;43656	chr2:178576084;178576083;178576082	chr2:179440811;179440810;179440809
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-129
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.2607
• 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
L/F	rs1390481050	-1.201	0.988	N	0.754	0.315	0.623733534801	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/F	rs1390481050	-1.201	0.988	N	0.754	0.315	0.623733534801	gnomAD-4.0.0	2.05299E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.47866E-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
L/A	0.9211	likely_pathogenic	0.908	pathogenic	-2.17	Highly Destabilizing	0.968	D	0.637	neutral	None	None	None	None	I
L/C	0.9389	likely_pathogenic	0.9186	pathogenic	-1.551	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
L/D	0.9932	likely_pathogenic	0.9912	pathogenic	-1.606	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	I
L/E	0.9711	likely_pathogenic	0.9647	pathogenic	-1.5	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	I
L/F	0.677	likely_pathogenic	0.6496	pathogenic	-1.323	Destabilizing	0.988	D	0.754	deleterious	N	0.504640792	None	None	I
L/G	0.9624	likely_pathogenic	0.9569	pathogenic	-2.617	Highly Destabilizing	0.995	D	0.743	deleterious	None	None	None	None	I
L/H	0.9377	likely_pathogenic	0.9216	pathogenic	-1.868	Destabilizing	0.999	D	0.755	deleterious	N	0.518813874	None	None	I
L/I	0.5284	ambiguous	0.47	ambiguous	-0.953	Destabilizing	0.919	D	0.569	neutral	D	0.527957582	None	None	I
L/K	0.9458	likely_pathogenic	0.9395	pathogenic	-1.644	Destabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	I
L/M	0.311	likely_benign	0.2946	benign	-0.856	Destabilizing	0.862	D	0.51	neutral	None	None	None	None	I
L/N	0.948	likely_pathogenic	0.9387	pathogenic	-1.607	Destabilizing	0.995	D	0.767	deleterious	None	None	None	None	I
L/P	0.9913	likely_pathogenic	0.9909	pathogenic	-1.331	Destabilizing	0.998	D	0.767	deleterious	N	0.518813874	None	None	I
L/Q	0.8879	likely_pathogenic	0.8599	pathogenic	-1.635	Destabilizing	0.995	D	0.745	deleterious	None	None	None	None	I
L/R	0.9295	likely_pathogenic	0.918	pathogenic	-1.188	Destabilizing	0.994	D	0.737	prob.delet.	N	0.518560385	None	None	I
L/S	0.9641	likely_pathogenic	0.9574	pathogenic	-2.359	Highly Destabilizing	0.991	D	0.711	prob.delet.	None	None	None	None	I
L/T	0.915	likely_pathogenic	0.8935	pathogenic	-2.116	Highly Destabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	I
L/V	0.5881	likely_pathogenic	0.5168	ambiguous	-1.331	Destabilizing	0.919	D	0.569	neutral	N	0.483171115	None	None	I
L/W	0.8586	likely_pathogenic	0.8382	pathogenic	-1.486	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
L/Y	0.8664	likely_pathogenic	0.8439	pathogenic	-1.261	Destabilizing	0.995	D	0.776	deleterious	None	None	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.