TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3097	9514;9515;9516	chr2:178768030;178768029;178768028	chr2:179632757;179632756;179632755
N2AB	3097	9514;9515;9516	chr2:178768030;178768029;178768028	chr2:179632757;179632756;179632755
N2A	3097	9514;9515;9516	chr2:178768030;178768029;178768028	chr2:179632757;179632756;179632755
N2B	3051	9376;9377;9378	chr2:178768030;178768029;178768028	chr2:179632757;179632756;179632755
Novex-1	3051	9376;9377;9378	chr2:178768030;178768029;178768028	chr2:179632757;179632756;179632755
Novex-2	3051	9376;9377;9378	chr2:178768030;178768029;178768028	chr2:179632757;179632756;179632755
Novex-3	3097	9514;9515;9516	chr2:178768030;178768029;178768028	chr2:179632757;179632756;179632755

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-21
• Domain position: 40
• Structural Position: 58
• Q(SASA): 0.2055
• 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/P	rs373366126	-1.515	1.0	D	0.879	0.837	None	gnomAD-2.1.1	2.83E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	5.43E-05	1.38543E-04
L/P	rs373366126	-1.515	1.0	D	0.879	0.837	None	gnomAD-3.1.2	5.91E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.17571E-04	0	0
L/P	rs373366126	-1.515	1.0	D	0.879	0.837	None	gnomAD-4.0.0	1.19576E-04	None	None	None	None	N	None	2.66923E-05	0	None	0	0	None	0	0	1.55081E-04	0	1.28033E-04
L/Q	None	-2.023	1.0	D	0.866	0.792	0.867437640688	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
L/Q	None	-2.023	1.0	D	0.866	0.792	0.867437640688	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
L/Q	None	-2.023	1.0	D	0.866	0.792	0.867437640688	gnomAD-4.0.0	6.57013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46964E-05	0	0
L/R	rs373366126	-1.241	1.0	D	0.875	0.821	0.865175587277	gnomAD-2.1.1	7.96E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.53E-05	None	0	0	0
L/R	rs373366126	-1.241	1.0	D	0.875	0.821	0.865175587277	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
L/R	rs373366126	-1.241	1.0	D	0.875	0.821	0.865175587277	gnomAD-4.0.0	2.47827E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.29359E-05	1.60041E-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	0.9197	likely_pathogenic	0.8958	pathogenic	-2.097	Highly Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
L/C	0.9246	likely_pathogenic	0.9243	pathogenic	-1.52	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
L/D	0.9964	likely_pathogenic	0.9946	pathogenic	-1.785	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/E	0.975	likely_pathogenic	0.9632	pathogenic	-1.65	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/F	0.5337	ambiguous	0.4779	ambiguous	-1.254	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
L/G	0.9825	likely_pathogenic	0.9766	pathogenic	-2.532	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/H	0.9488	likely_pathogenic	0.9294	pathogenic	-1.608	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/I	0.1172	likely_benign	0.1062	benign	-0.899	Destabilizing	0.999	D	0.505	neutral	None	None	None	None	N
L/K	0.9562	likely_pathogenic	0.9431	pathogenic	-1.666	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/M	0.2371	likely_benign	0.2296	benign	-0.883	Destabilizing	1.0	D	0.739	prob.delet.	D	0.652668106	None	None	N
L/N	0.977	likely_pathogenic	0.9692	pathogenic	-1.797	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/P	0.9772	likely_pathogenic	0.9627	pathogenic	-1.273	Destabilizing	1.0	D	0.879	deleterious	D	0.736070716	None	None	N
L/Q	0.9096	likely_pathogenic	0.8728	pathogenic	-1.777	Destabilizing	1.0	D	0.866	deleterious	D	0.736484018	None	None	N
L/R	0.9422	likely_pathogenic	0.9198	pathogenic	-1.218	Destabilizing	1.0	D	0.875	deleterious	D	0.772777184	None	None	N
L/S	0.9771	likely_pathogenic	0.9658	pathogenic	-2.467	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/T	0.9099	likely_pathogenic	0.8836	pathogenic	-2.185	Highly Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/V	0.2219	likely_benign	0.1986	benign	-1.273	Destabilizing	0.999	D	0.502	neutral	N	0.513348375	None	None	N
L/W	0.8477	likely_pathogenic	0.8193	pathogenic	-1.394	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/Y	0.8943	likely_pathogenic	0.8795	pathogenic	-1.166	Destabilizing	1.0	D	0.856	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.