TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28284	85075;85076;85077	chr2:178561282;178561281;178561280	chr2:179426009;179426008;179426007
N2AB	26643	80152;80153;80154	chr2:178561282;178561281;178561280	chr2:179426009;179426008;179426007
N2A	25716	77371;77372;77373	chr2:178561282;178561281;178561280	chr2:179426009;179426008;179426007
N2B	19219	57880;57881;57882	chr2:178561282;178561281;178561280	chr2:179426009;179426008;179426007
Novex-1	19344	58255;58256;58257	chr2:178561282;178561281;178561280	chr2:179426009;179426008;179426007
Novex-2	19411	58456;58457;58458	chr2:178561282;178561281;178561280	chr2:179426009;179426008;179426007
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-94
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1427
• 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
I/T	rs1462392007	None	0.896	N	0.724	0.53	0.72338399144	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	5.65419E-05	0	None	0	0	None	0	0	0	0	0
I/V	rs1408628454	None	0.004	N	0.181	0.127	0.416075642716	gnomAD-4.0.0	3.18249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71611E-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
I/A	0.9652	likely_pathogenic	0.9714	pathogenic	-2.266	Highly Destabilizing	0.702	D	0.686	prob.neutral	None	None	None	None	N
I/C	0.9676	likely_pathogenic	0.9728	pathogenic	-1.457	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
I/D	0.9961	likely_pathogenic	0.9955	pathogenic	-2.409	Highly Destabilizing	0.996	D	0.834	deleterious	None	None	None	None	N
I/E	0.9886	likely_pathogenic	0.9887	pathogenic	-2.362	Highly Destabilizing	0.988	D	0.817	deleterious	None	None	None	None	N
I/F	0.8435	likely_pathogenic	0.8807	pathogenic	-1.678	Destabilizing	0.984	D	0.739	prob.delet.	D	0.530297268	None	None	N
I/G	0.9918	likely_pathogenic	0.9928	pathogenic	-2.655	Highly Destabilizing	0.988	D	0.819	deleterious	None	None	None	None	N
I/H	0.9898	likely_pathogenic	0.9905	pathogenic	-1.985	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
I/K	0.9776	likely_pathogenic	0.9808	pathogenic	-1.718	Destabilizing	0.988	D	0.817	deleterious	None	None	None	None	N
I/L	0.3448	ambiguous	0.3951	ambiguous	-1.221	Destabilizing	0.437	N	0.441	neutral	N	0.519620526	None	None	N
I/M	0.4175	ambiguous	0.4715	ambiguous	-0.847	Destabilizing	0.984	D	0.701	prob.neutral	D	0.544188468	None	None	N
I/N	0.8915	likely_pathogenic	0.8455	pathogenic	-1.642	Destabilizing	0.995	D	0.827	deleterious	D	0.527262755	None	None	N
I/P	0.9431	likely_pathogenic	0.9488	pathogenic	-1.543	Destabilizing	0.996	D	0.835	deleterious	None	None	None	None	N
I/Q	0.9829	likely_pathogenic	0.9842	pathogenic	-1.802	Destabilizing	0.996	D	0.83	deleterious	None	None	None	None	N
I/R	0.9742	likely_pathogenic	0.9786	pathogenic	-1.083	Destabilizing	0.988	D	0.828	deleterious	None	None	None	None	N
I/S	0.9651	likely_pathogenic	0.9671	pathogenic	-2.225	Highly Destabilizing	0.984	D	0.791	deleterious	D	0.529464801	None	None	N
I/T	0.9332	likely_pathogenic	0.9375	pathogenic	-2.062	Highly Destabilizing	0.896	D	0.724	prob.delet.	N	0.519754337	None	None	N
I/V	0.1279	likely_benign	0.1322	benign	-1.543	Destabilizing	0.004	N	0.181	neutral	N	0.481043495	None	None	N
I/W	0.9947	likely_pathogenic	0.9955	pathogenic	-1.887	Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
I/Y	0.9668	likely_pathogenic	0.9725	pathogenic	-1.673	Destabilizing	0.996	D	0.797	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.