TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29116	87571;87572;87573	chr2:178558008;178558007;178558006	chr2:179422735;179422734;179422733
N2AB	27475	82648;82649;82650	chr2:178558008;178558007;178558006	chr2:179422735;179422734;179422733
N2A	26548	79867;79868;79869	chr2:178558008;178558007;178558006	chr2:179422735;179422734;179422733
N2B	20051	60376;60377;60378	chr2:178558008;178558007;178558006	chr2:179422735;179422734;179422733
Novex-1	20176	60751;60752;60753	chr2:178558008;178558007;178558006	chr2:179422735;179422734;179422733
Novex-2	20243	60952;60953;60954	chr2:178558008;178558007;178558006	chr2:179422735;179422734;179422733
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-145
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.2399
• 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
E/G	None	None	0.896	N	0.558	0.279	0.276482976112	gnomAD-4.0.0	6.84218E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65645E-05
E/K	rs1472877475	-0.663	0.896	N	0.476	0.192	0.191931220699	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14784E-04	0	None	0	0	None	0	None	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
E/A	0.2102	likely_benign	0.2002	benign	-0.899	Destabilizing	0.896	D	0.491	neutral	N	0.483432361	None	None	N
E/C	0.8243	likely_pathogenic	0.805	pathogenic	-0.571	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
E/D	0.1217	likely_benign	0.1083	benign	-1.382	Destabilizing	0.004	N	0.222	neutral	N	0.45449632	None	None	N
E/F	0.7468	likely_pathogenic	0.7207	pathogenic	-0.989	Destabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
E/G	0.2418	likely_benign	0.2478	benign	-1.223	Destabilizing	0.896	D	0.558	neutral	N	0.476314387	None	None	N
E/H	0.4564	ambiguous	0.4109	ambiguous	-1.264	Destabilizing	0.996	D	0.544	neutral	None	None	None	None	N
E/I	0.3598	ambiguous	0.3354	benign	-0.025	Destabilizing	0.988	D	0.774	deleterious	None	None	None	None	N
E/K	0.2551	likely_benign	0.2492	benign	-0.663	Destabilizing	0.896	D	0.476	neutral	N	0.441431022	None	None	N
E/L	0.4404	ambiguous	0.4058	ambiguous	-0.025	Destabilizing	0.988	D	0.709	prob.delet.	None	None	None	None	N
E/M	0.4764	ambiguous	0.4538	ambiguous	0.469	Stabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
E/N	0.2554	likely_benign	0.2346	benign	-0.944	Destabilizing	0.851	D	0.473	neutral	None	None	None	None	N
E/P	0.9309	likely_pathogenic	0.9198	pathogenic	-0.296	Destabilizing	0.988	D	0.591	neutral	None	None	None	None	N
E/Q	0.1724	likely_benign	0.1644	benign	-0.854	Destabilizing	0.946	D	0.523	neutral	N	0.483259002	None	None	N
E/R	0.3832	ambiguous	0.3608	ambiguous	-0.646	Destabilizing	0.988	D	0.52	neutral	None	None	None	None	N
E/S	0.2159	likely_benign	0.1994	benign	-1.342	Destabilizing	0.919	D	0.468	neutral	None	None	None	None	N
E/T	0.2387	likely_benign	0.2201	benign	-1.053	Destabilizing	0.919	D	0.54	neutral	None	None	None	None	N
E/V	0.2303	likely_benign	0.2108	benign	-0.296	Destabilizing	0.984	D	0.611	neutral	N	0.459843425	None	None	N
E/W	0.9037	likely_pathogenic	0.88	pathogenic	-0.973	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/Y	0.6048	likely_pathogenic	0.5693	pathogenic	-0.754	Destabilizing	0.996	D	0.734	prob.delet.	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.