TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4861	14806;14807;14808	chr2:178735865;178735864;178735863	chr2:179600592;179600591;179600590
N2AB	4544	13855;13856;13857	chr2:178735865;178735864;178735863	chr2:179600592;179600591;179600590
N2A	3617	11074;11075;11076	chr2:178735865;178735864;178735863	chr2:179600592;179600591;179600590
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-31
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1299
• 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/G	rs566100734	None	0.805	D	0.701	0.815	0.0954503805726	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85796E-06	0	0
D/V	rs566100734	2.747	0.983	D	0.854	0.852	0.195762928549	gnomAD-2.1.1	4.64E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.92157E-04	None	0	7.8E-06	0
D/V	rs566100734	2.747	0.983	D	0.854	0.852	0.195762928549	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
D/V	rs566100734	2.747	0.983	D	0.854	0.852	0.195762928549	gnomAD-4.0.0	3.45855E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.39269E-06	3.48413E-04	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	0.6544	likely_pathogenic	0.5502	ambiguous	0.612	Stabilizing	0.892	D	0.798	deleterious	D	0.711650531	None	None	N
D/C	0.8929	likely_pathogenic	0.8394	pathogenic	0.374	Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
D/E	0.4794	ambiguous	0.3967	ambiguous	-0.551	Destabilizing	0.892	D	0.628	neutral	D	0.663240541	None	None	N
D/F	0.932	likely_pathogenic	0.8846	pathogenic	1.347	Stabilizing	0.987	D	0.849	deleterious	None	None	None	None	N
D/G	0.5349	ambiguous	0.4402	ambiguous	0.16	Stabilizing	0.805	D	0.701	prob.neutral	D	0.782618466	None	None	N
D/H	0.5754	likely_pathogenic	0.4484	ambiguous	1.044	Stabilizing	0.025	N	0.523	neutral	D	0.56628007	None	None	N
D/I	0.9197	likely_pathogenic	0.8707	pathogenic	1.817	Stabilizing	0.987	D	0.837	deleterious	None	None	None	None	N
D/K	0.8493	likely_pathogenic	0.8001	pathogenic	0.375	Stabilizing	0.975	D	0.777	deleterious	None	None	None	None	N
D/L	0.8896	likely_pathogenic	0.8393	pathogenic	1.817	Stabilizing	0.987	D	0.853	deleterious	None	None	None	None	N
D/M	0.9342	likely_pathogenic	0.8935	pathogenic	2.033	Highly Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
D/N	0.2707	likely_benign	0.2065	benign	-0.493	Destabilizing	0.025	N	0.379	neutral	D	0.615645611	None	None	N
D/P	0.9863	likely_pathogenic	0.9792	pathogenic	1.446	Stabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
D/Q	0.7218	likely_pathogenic	0.6285	pathogenic	-0.158	Destabilizing	0.975	D	0.721	prob.delet.	None	None	None	None	N
D/R	0.9013	likely_pathogenic	0.8668	pathogenic	0.425	Stabilizing	0.975	D	0.83	deleterious	None	None	None	None	N
D/S	0.4589	ambiguous	0.3572	ambiguous	-0.707	Destabilizing	0.845	D	0.647	neutral	None	None	None	None	N
D/T	0.8314	likely_pathogenic	0.7498	pathogenic	-0.289	Destabilizing	0.975	D	0.788	deleterious	None	None	None	None	N
D/V	0.8056	likely_pathogenic	0.7321	pathogenic	1.446	Stabilizing	0.983	D	0.854	deleterious	D	0.747288915	None	None	N
D/W	0.9782	likely_pathogenic	0.9653	pathogenic	1.388	Stabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
D/Y	0.5423	ambiguous	0.4494	ambiguous	1.622	Stabilizing	0.967	D	0.853	deleterious	D	0.643659131	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.