TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9916	29971;29972;29973	chr2:178704726;178704725;178704724	chr2:179569453;179569452;179569451
N2AB	9599	29020;29021;29022	chr2:178704726;178704725;178704724	chr2:179569453;179569452;179569451
N2A	8672	26239;26240;26241	chr2:178704726;178704725;178704724	chr2:179569453;179569452;179569451
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-84
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.2884
• 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
D/E	rs990983452	-0.544	None	None	0.118	0.029	0.208816687407	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
D/E	rs990983452	-0.544	None	None	0.118	0.029	0.208816687407	gnomAD-4.0.0	6.85456E-07	None	None	None	None	N	None	0	2.24296E-05	None	0	0	None	0	0	0	0	0
D/G	rs768314420	-0.584	0.22	None	0.449	0.196	0.225215365344	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	1.67485E-04	None	0	None	0	0	0
D/G	rs768314420	-0.584	0.22	None	0.449	0.196	0.225215365344	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
D/G	rs768314420	-0.584	0.22	None	0.449	0.196	0.225215365344	gnomAD-4.0.0	5.14235E-06	None	None	None	None	N	None	0	0	None	0	9.69556E-05	None	0	0	0	0	0
D/N	None	None	0.22	None	0.449	0.176	0.240491677333	gnomAD-4.0.0	1.59866E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.96665E-05	0	0	0	0
D/V	rs768314420	0.248	0.001	None	0.403	0.221	0.31411915649	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
D/V	rs768314420	0.248	0.001	None	0.403	0.221	0.31411915649	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92456E-04	None	0	0	0	0	0
D/V	rs768314420	0.248	0.001	None	0.403	0.221	0.31411915649	gnomAD-4.0.0	3.59965E-05	None	None	None	None	N	None	0	0	None	0	6.78689E-04	None	0	0	0	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
D/A	0.3342	likely_benign	0.5339	ambiguous	-0.301	Destabilizing	0.124	N	0.525	neutral	None	None	None	None	N
D/C	0.8483	likely_pathogenic	0.9374	pathogenic	-0.007	Destabilizing	0.968	D	0.699	prob.neutral	None	None	None	None	N
D/E	0.2887	likely_benign	0.4671	ambiguous	-0.656	Destabilizing	None	N	0.118	neutral	None	None	None	None	N
D/F	0.8679	likely_pathogenic	0.9343	pathogenic	-0.357	Destabilizing	0.726	D	0.669	neutral	None	None	None	None	N
D/G	0.4634	ambiguous	0.6679	pathogenic	-0.577	Destabilizing	0.22	N	0.449	neutral	None	None	None	None	N
D/H	0.4955	ambiguous	0.693	pathogenic	-0.705	Destabilizing	0.667	D	0.571	neutral	None	None	None	None	N
D/I	0.6334	likely_pathogenic	0.809	pathogenic	0.394	Stabilizing	0.396	N	0.579	neutral	None	None	None	None	N
D/K	0.6574	likely_pathogenic	0.8542	pathogenic	-0.247	Destabilizing	0.157	N	0.455	neutral	None	None	None	None	N
D/L	0.7267	likely_pathogenic	0.8663	pathogenic	0.394	Stabilizing	0.157	N	0.568	neutral	None	None	None	None	N
D/M	0.8715	likely_pathogenic	0.9463	pathogenic	0.802	Stabilizing	0.909	D	0.663	neutral	None	None	None	None	N
D/N	0.1648	likely_benign	0.2265	benign	-0.469	Destabilizing	0.22	N	0.449	neutral	None	None	None	None	N
D/P	0.8796	likely_pathogenic	0.9375	pathogenic	0.188	Stabilizing	0.726	D	0.533	neutral	None	None	None	None	N
D/Q	0.6285	likely_pathogenic	0.8255	pathogenic	-0.388	Destabilizing	0.396	N	0.432	neutral	None	None	None	None	N
D/R	0.6931	likely_pathogenic	0.8754	pathogenic	-0.199	Destabilizing	0.396	N	0.629	neutral	None	None	None	None	N
D/S	0.232	likely_benign	0.3519	ambiguous	-0.646	Destabilizing	0.157	N	0.393	neutral	None	None	None	None	N
D/T	0.3938	ambiguous	0.5707	pathogenic	-0.437	Destabilizing	0.272	N	0.49	neutral	None	None	None	None	N
D/V	0.4122	ambiguous	0.626	pathogenic	0.188	Stabilizing	0.001	N	0.403	neutral	None	None	None	None	N
D/W	0.973	likely_pathogenic	0.9882	pathogenic	-0.336	Destabilizing	0.968	D	0.719	prob.delet.	None	None	None	None	N
D/Y	0.519	ambiguous	0.6948	pathogenic	-0.173	Destabilizing	0.859	D	0.669	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.