TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23925	71998;71999;72000	chr2:178574359;178574358;178574357	chr2:179439086;179439085;179439084
N2AB	22284	67075;67076;67077	chr2:178574359;178574358;178574357	chr2:179439086;179439085;179439084
N2A	21357	64294;64295;64296	chr2:178574359;178574358;178574357	chr2:179439086;179439085;179439084
N2B	14860	44803;44804;44805	chr2:178574359;178574358;178574357	chr2:179439086;179439085;179439084
Novex-1	14985	45178;45179;45180	chr2:178574359;178574358;178574357	chr2:179439086;179439085;179439084
Novex-2	15052	45379;45380;45381	chr2:178574359;178574358;178574357	chr2:179439086;179439085;179439084
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: Fn3-62
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2174
• 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/M	rs1401717606	-0.74	0.93	N	0.545	0.146	0.0762999501168	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/M	rs1401717606	-0.74	0.93	N	0.545	0.146	0.0762999501168	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/M	rs1401717606	-0.74	0.93	N	0.545	0.146	0.0762999501168	gnomAD-4.0.0	2.10725E-05	None	None	None	None	N	None	2.67023E-05	0	None	0	0	None	0	0	2.71264E-05	0	0
I/N	rs374887185	-1.259	0.976	N	0.671	0.382	None	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
I/N	rs374887185	-1.259	0.976	N	0.671	0.382	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20697E-04	0	0	0	0	None	0	0	0	0	0
I/N	rs374887185	-1.259	0.976	N	0.671	0.382	None	gnomAD-4.0.0	3.71871E-06	None	None	None	None	N	None	8.01239E-05	0	None	0	0	None	0	0	0	0	0
I/T	rs374887185	-1.797	0.651	N	0.579	0.293	0.317378411342	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	2.9E-05	None	0	5.58E-05	None	0	None	0	8.88E-06	0
I/T	rs374887185	-1.797	0.651	N	0.579	0.293	0.317378411342	gnomAD-4.0.0	6.84282E-06	None	None	None	None	N	None	0	2.23624E-05	None	0	0	None	0	0	8.0959E-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	0.3319	likely_benign	0.3685	ambiguous	-2.341	Highly Destabilizing	0.338	N	0.495	neutral	None	None	None	None	N
I/C	0.7708	likely_pathogenic	0.7755	pathogenic	-1.846	Destabilizing	0.018	N	0.284	neutral	None	None	None	None	N
I/D	0.9806	likely_pathogenic	0.9807	pathogenic	-2.977	Highly Destabilizing	0.982	D	0.613	neutral	None	None	None	None	N
I/E	0.9574	likely_pathogenic	0.9578	pathogenic	-2.872	Highly Destabilizing	0.982	D	0.601	neutral	None	None	None	None	N
I/F	0.7098	likely_pathogenic	0.6918	pathogenic	-1.421	Destabilizing	0.93	D	0.567	neutral	N	0.47240729	None	None	N
I/G	0.8827	likely_pathogenic	0.9046	pathogenic	-2.746	Highly Destabilizing	0.946	D	0.608	neutral	None	None	None	None	N
I/H	0.9738	likely_pathogenic	0.9725	pathogenic	-2.001	Highly Destabilizing	0.995	D	0.604	neutral	None	None	None	None	N
I/K	0.9491	likely_pathogenic	0.9429	pathogenic	-1.719	Destabilizing	0.982	D	0.598	neutral	None	None	None	None	N
I/L	0.2328	likely_benign	0.2413	benign	-1.213	Destabilizing	0.144	N	0.37	neutral	N	0.467980119	None	None	N
I/M	0.1838	likely_benign	0.1864	benign	-1.231	Destabilizing	0.93	D	0.545	neutral	N	0.460830221	None	None	N
I/N	0.8307	likely_pathogenic	0.8256	pathogenic	-1.865	Destabilizing	0.976	D	0.671	prob.neutral	N	0.472440016	None	None	N
I/P	0.864	likely_pathogenic	0.8328	pathogenic	-1.568	Destabilizing	0.982	D	0.672	prob.neutral	None	None	None	None	N
I/Q	0.9383	likely_pathogenic	0.9345	pathogenic	-1.947	Destabilizing	0.982	D	0.63	neutral	None	None	None	None	N
I/R	0.9233	likely_pathogenic	0.9183	pathogenic	-1.223	Destabilizing	0.982	D	0.661	prob.neutral	None	None	None	None	N
I/S	0.5955	likely_pathogenic	0.6206	pathogenic	-2.422	Highly Destabilizing	0.651	D	0.458	neutral	N	0.453068313	None	None	N
I/T	0.19	likely_benign	0.2082	benign	-2.204	Highly Destabilizing	0.651	D	0.579	neutral	N	0.511866969	None	None	N
I/V	0.0579	likely_benign	0.0641	benign	-1.568	Destabilizing	0.003	N	0.083	neutral	N	0.426557571	None	None	N
I/W	0.9907	likely_pathogenic	0.9895	pathogenic	-1.692	Destabilizing	0.995	D	0.658	prob.neutral	None	None	None	None	N
I/Y	0.9674	likely_pathogenic	0.9614	pathogenic	-1.484	Destabilizing	0.982	D	0.597	neutral	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.