TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1570	4933;4934;4935	chr2:178777255;178777254;178777253	chr2:179641982;179641981;179641980
N2AB	1570	4933;4934;4935	chr2:178777255;178777254;178777253	chr2:179641982;179641981;179641980
N2A	1570	4933;4934;4935	chr2:178777255;178777254;178777253	chr2:179641982;179641981;179641980
N2B	1524	4795;4796;4797	chr2:178777255;178777254;178777253	chr2:179641982;179641981;179641980
Novex-1	1524	4795;4796;4797	chr2:178777255;178777254;178777253	chr2:179641982;179641981;179641980
Novex-2	1524	4795;4796;4797	chr2:178777255;178777254;178777253	chr2:179641982;179641981;179641980
Novex-3	1570	4933;4934;4935	chr2:178777255;178777254;178777253	chr2:179641982;179641981;179641980

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-7
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.4627
• 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
G/A	rs199910114	-0.13	1.0	D	0.759	0.734	None	gnomAD-2.1.1	6.38E-05	None	None	None	None	N	None	6.00913E-04	8.47E-05	None	0	0	None	0	None	0	0	0
G/A	rs199910114	-0.13	1.0	D	0.759	0.734	None	gnomAD-3.1.2	9.86E-05	None	None	None	None	N	None	2.89464E-04	1.30941E-04	0	0	0	None	0	0	0	0	4.78011E-04
G/A	rs199910114	-0.13	1.0	D	0.759	0.734	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
G/A	rs199910114	-0.13	1.0	D	0.759	0.734	None	gnomAD-4.0.0	2.35433E-05	None	None	None	None	N	None	3.86409E-04	9.99867E-05	None	0	0	None	0	0	0	0	4.79969E-05
G/C	None	None	1.0	D	0.792	0.836	0.888038843388	gnomAD-4.0.0	3.18143E-06	None	None	None	None	N	None	5.65419E-05	0	None	0	0	None	0	0	2.85673E-06	0	0
G/D	None	None	1.0	D	0.825	0.769	0.689628011126	gnomAD-4.0.0	6.84106E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99319E-07	0	0
G/S	rs1405416253	-0.333	1.0	D	0.787	0.721	0.652782900136	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
G/S	rs1405416253	-0.333	1.0	D	0.787	0.721	0.652782900136	gnomAD-4.0.0	1.59072E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	None	0	0	0	0	0
G/V	rs199910114	None	1.0	D	0.791	0.809	0.857513295568	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
G/V	rs199910114	None	1.0	D	0.791	0.809	0.857513295568	gnomAD-4.0.0	2.47842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.38991E-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
G/A	0.3682	ambiguous	0.3259	benign	-0.221	Destabilizing	1.0	D	0.759	deleterious	D	0.719779615	None	None	N
G/C	0.6398	likely_pathogenic	0.5605	ambiguous	-0.866	Destabilizing	1.0	D	0.792	deleterious	D	0.776535402	None	None	N
G/D	0.3747	ambiguous	0.3213	benign	-0.349	Destabilizing	1.0	D	0.825	deleterious	D	0.646238701	None	None	N
G/E	0.4807	ambiguous	0.4059	ambiguous	-0.511	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
G/F	0.8536	likely_pathogenic	0.8304	pathogenic	-1.001	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
G/H	0.6379	likely_pathogenic	0.5867	pathogenic	-0.447	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/I	0.8333	likely_pathogenic	0.7879	pathogenic	-0.406	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/K	0.6293	likely_pathogenic	0.5573	ambiguous	-0.53	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/L	0.8027	likely_pathogenic	0.7726	pathogenic	-0.406	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/M	0.8141	likely_pathogenic	0.7827	pathogenic	-0.381	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/N	0.3275	likely_benign	0.2987	benign	-0.28	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
G/P	0.9899	likely_pathogenic	0.9858	pathogenic	-0.314	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/Q	0.5717	likely_pathogenic	0.5164	ambiguous	-0.569	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/R	0.552	ambiguous	0.4944	ambiguous	-0.158	Destabilizing	1.0	D	0.83	deleterious	D	0.719861418	None	None	N
G/S	0.218	likely_benign	0.197	benign	-0.447	Destabilizing	1.0	D	0.787	deleterious	D	0.692889895	None	None	N
G/T	0.51	ambiguous	0.4517	ambiguous	-0.538	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
G/V	0.7304	likely_pathogenic	0.6762	pathogenic	-0.314	Destabilizing	1.0	D	0.791	deleterious	D	0.776779228	None	None	N
G/W	0.7995	likely_pathogenic	0.7601	pathogenic	-1.128	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
G/Y	0.734	likely_pathogenic	0.6886	pathogenic	-0.763	Destabilizing	1.0	D	0.8	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.