TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5276	16051;16052;16053	chr2:178733467;178733466;178733465	chr2:179598194;179598193;179598192
N2AB	4959	15100;15101;15102	chr2:178733467;178733466;178733465	chr2:179598194;179598193;179598192
N2A	4032	12319;12320;12321	chr2:178733467;178733466;178733465	chr2:179598194;179598193;179598192
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-36
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.8781
• Predicted PPI site: I

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/N	rs769246267	0.592	0.993	N	0.719	0.226	0.158396225186	gnomAD-2.1.1	7.15E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
D/N	rs769246267	0.592	0.993	N	0.719	0.226	0.158396225186	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs769246267	0.592	0.993	N	0.719	0.226	0.158396225186	gnomAD-4.0.0	2.47888E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.39055E-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
D/A	0.4855	ambiguous	0.4721	ambiguous	-0.227	Destabilizing	0.977	D	0.635	neutral	N	0.490828993	None	None	I
D/C	0.9115	likely_pathogenic	0.9113	pathogenic	0.255	Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
D/E	0.3012	likely_benign	0.3108	benign	-0.274	Destabilizing	0.117	N	0.302	neutral	N	0.435857425	None	None	I
D/F	0.7685	likely_pathogenic	0.759	pathogenic	-0.351	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
D/G	0.6861	likely_pathogenic	0.6769	pathogenic	-0.399	Destabilizing	0.989	D	0.682	prob.neutral	N	0.440529099	None	None	I
D/H	0.6405	likely_pathogenic	0.5934	pathogenic	-0.268	Destabilizing	0.999	D	0.717	prob.delet.	N	0.504400287	None	None	I
D/I	0.621	likely_pathogenic	0.624	pathogenic	0.172	Stabilizing	0.998	D	0.79	deleterious	None	None	None	None	I
D/K	0.7814	likely_pathogenic	0.7352	pathogenic	0.486	Stabilizing	0.99	D	0.714	prob.delet.	None	None	None	None	I
D/L	0.6494	likely_pathogenic	0.642	pathogenic	0.172	Stabilizing	0.995	D	0.759	deleterious	None	None	None	None	I
D/M	0.7884	likely_pathogenic	0.7817	pathogenic	0.398	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
D/N	0.1947	likely_benign	0.1837	benign	0.266	Stabilizing	0.993	D	0.719	prob.delet.	N	0.455444452	None	None	I
D/P	0.9851	likely_pathogenic	0.9858	pathogenic	0.061	Stabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
D/Q	0.6303	likely_pathogenic	0.598	pathogenic	0.272	Stabilizing	0.99	D	0.748	deleterious	None	None	None	None	I
D/R	0.8163	likely_pathogenic	0.7898	pathogenic	0.523	Stabilizing	0.995	D	0.746	deleterious	None	None	None	None	I
D/S	0.3167	likely_benign	0.3006	benign	0.168	Stabilizing	0.983	D	0.642	neutral	None	None	None	None	I
D/T	0.5994	likely_pathogenic	0.5801	pathogenic	0.3	Stabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	I
D/V	0.4702	ambiguous	0.4636	ambiguous	0.061	Stabilizing	0.997	D	0.761	deleterious	D	0.599931545	None	None	I
D/W	0.9687	likely_pathogenic	0.9647	pathogenic	-0.273	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
D/Y	0.4594	ambiguous	0.4179	ambiguous	-0.119	Destabilizing	1.0	D	0.779	deleterious	D	0.524483792	None	None	I

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.