TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8281	25066;25067;25068	chr2:178718165;178718164;178718163	chr2:179582892;179582891;179582890
N2AB	7964	24115;24116;24117	chr2:178718165;178718164;178718163	chr2:179582892;179582891;179582890
N2A	7037	21334;21335;21336	chr2:178718165;178718164;178718163	chr2:179582892;179582891;179582890
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-68
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2053
• 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
A/E	rs1474165122	-1.112	0.055	D	0.689	0.374	0.186928172975	gnomAD-2.1.1	8.22E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.55E-05	None	0	0	0
A/E	rs1474165122	-1.112	0.055	D	0.689	0.374	0.186928172975	gnomAD-4.0.0	4.83065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.30108E-05	0
A/T	rs2077783832	None	None	N	0.183	0.211	0.0401082797425	gnomAD-4.0.0	1.61075E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86054E-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
A/C	0.4588	ambiguous	0.4356	ambiguous	-0.903	Destabilizing	0.676	D	0.664	neutral	None	None	None	None	I
A/D	0.7123	likely_pathogenic	0.8112	pathogenic	-0.942	Destabilizing	0.214	N	0.739	prob.delet.	None	None	None	None	I
A/E	0.5176	ambiguous	0.6234	pathogenic	-0.937	Destabilizing	0.055	N	0.689	prob.neutral	D	0.54967783	None	None	I
A/F	0.342	ambiguous	0.3706	ambiguous	-0.793	Destabilizing	0.214	N	0.734	prob.delet.	None	None	None	None	I
A/G	0.2845	likely_benign	0.3171	benign	-1.094	Destabilizing	0.055	N	0.591	neutral	N	0.494453239	None	None	I
A/H	0.6964	likely_pathogenic	0.7718	pathogenic	-1.273	Destabilizing	0.864	D	0.689	prob.neutral	None	None	None	None	I
A/I	0.1455	likely_benign	0.1217	benign	-0.118	Destabilizing	None	N	0.461	neutral	None	None	None	None	I
A/K	0.6177	likely_pathogenic	0.7173	pathogenic	-1.159	Destabilizing	0.072	N	0.691	prob.neutral	None	None	None	None	I
A/L	0.1356	likely_benign	0.134	benign	-0.118	Destabilizing	None	N	0.405	neutral	None	None	None	None	I
A/M	0.1826	likely_benign	0.1722	benign	-0.188	Destabilizing	0.214	N	0.716	prob.delet.	None	None	None	None	I
A/N	0.5371	ambiguous	0.6149	pathogenic	-0.946	Destabilizing	0.214	N	0.735	prob.delet.	None	None	None	None	I
A/P	0.8175	likely_pathogenic	0.8828	pathogenic	-0.299	Destabilizing	None	N	0.467	neutral	D	0.538321524	None	None	I
A/Q	0.5156	ambiguous	0.6084	pathogenic	-1.018	Destabilizing	0.356	N	0.75	deleterious	None	None	None	None	I
A/R	0.5227	ambiguous	0.6329	pathogenic	-0.905	Destabilizing	0.214	N	0.751	deleterious	None	None	None	None	I
A/S	0.1601	likely_benign	0.1813	benign	-1.351	Destabilizing	0.012	N	0.551	neutral	N	0.51971029	None	None	I
A/T	0.076	likely_benign	0.0736	benign	-1.233	Destabilizing	None	N	0.183	neutral	N	0.493199018	None	None	I
A/V	0.074	likely_benign	0.0642	benign	-0.299	Destabilizing	None	N	0.227	neutral	N	0.450539735	None	None	I
A/W	0.802	likely_pathogenic	0.8486	pathogenic	-1.196	Destabilizing	0.864	D	0.722	prob.delet.	None	None	None	None	I
A/Y	0.5939	likely_pathogenic	0.6507	pathogenic	-0.749	Destabilizing	0.356	N	0.739	prob.delet.	None	None	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.