TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32482	97669;97670;97671	chr2:178542312;178542311;178542310	chr2:179407039;179407038;179407037
N2AB	30841	92746;92747;92748	chr2:178542312;178542311;178542310	chr2:179407039;179407038;179407037
N2A	29914	89965;89966;89967	chr2:178542312;178542311;178542310	chr2:179407039;179407038;179407037
N2B	23417	70474;70475;70476	chr2:178542312;178542311;178542310	chr2:179407039;179407038;179407037
Novex-1	23542	70849;70850;70851	chr2:178542312;178542311;178542310	chr2:179407039;179407038;179407037
Novex-2	23609	71050;71051;71052	chr2:178542312;178542311;178542310	chr2:179407039;179407038;179407037
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-124
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3735
• 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
I/T	rs773555433	-1.291	0.892	N	0.726	0.238	0.592138549	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.69E-05	0
I/T	rs773555433	-1.291	0.892	N	0.726	0.238	0.592138549	gnomAD-4.0.0	2.46521E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.87575E-05	0	2.87955E-05	1.16268E-05	3.3151E-05

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	0.2849	likely_benign	0.2266	benign	-1.457	Destabilizing	0.845	D	0.659	neutral	None	None	None	None	I
I/C	0.7526	likely_pathogenic	0.7045	pathogenic	-1.005	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
I/D	0.8795	likely_pathogenic	0.8501	pathogenic	-0.306	Destabilizing	0.996	D	0.853	deleterious	None	None	None	None	I
I/E	0.735	likely_pathogenic	0.6883	pathogenic	-0.311	Destabilizing	0.987	D	0.849	deleterious	None	None	None	None	I
I/F	0.266	likely_benign	0.2338	benign	-1.017	Destabilizing	0.967	D	0.771	deleterious	N	0.43753786	None	None	I
I/G	0.7704	likely_pathogenic	0.6889	pathogenic	-1.758	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	I
I/H	0.6981	likely_pathogenic	0.6449	pathogenic	-0.813	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	I
I/K	0.539	ambiguous	0.484	ambiguous	-0.739	Destabilizing	0.987	D	0.846	deleterious	None	None	None	None	I
I/L	0.1896	likely_benign	0.1607	benign	-0.722	Destabilizing	0.426	N	0.384	neutral	N	0.42454992	None	None	I
I/M	0.1444	likely_benign	0.1234	benign	-0.636	Destabilizing	0.983	D	0.769	deleterious	N	0.444695906	None	None	I
I/N	0.5024	ambiguous	0.445	ambiguous	-0.549	Destabilizing	0.994	D	0.855	deleterious	N	0.473669232	None	None	I
I/P	0.6488	likely_pathogenic	0.5735	pathogenic	-0.934	Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	I
I/Q	0.5859	likely_pathogenic	0.5348	ambiguous	-0.717	Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	I
I/R	0.4415	ambiguous	0.3875	ambiguous	-0.187	Destabilizing	0.987	D	0.851	deleterious	None	None	None	None	I
I/S	0.387	ambiguous	0.3339	benign	-1.278	Destabilizing	0.967	D	0.818	deleterious	N	0.465839182	None	None	I
I/T	0.1309	likely_benign	0.1098	benign	-1.155	Destabilizing	0.892	D	0.726	prob.delet.	N	0.392304216	None	None	I
I/V	0.0843	likely_benign	0.0779	benign	-0.934	Destabilizing	0.011	N	0.285	neutral	N	0.352977824	None	None	I
I/W	0.8653	likely_pathogenic	0.8338	pathogenic	-0.987	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
I/Y	0.7013	likely_pathogenic	0.6508	pathogenic	-0.772	Destabilizing	0.987	D	0.803	deleterious	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.