TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27440	82543;82544;82545	chr2:178563814;178563813;178563812	chr2:179428541;179428540;179428539
N2AB	25799	77620;77621;77622	chr2:178563814;178563813;178563812	chr2:179428541;179428540;179428539
N2A	24872	74839;74840;74841	chr2:178563814;178563813;178563812	chr2:179428541;179428540;179428539
N2B	18375	55348;55349;55350	chr2:178563814;178563813;178563812	chr2:179428541;179428540;179428539
Novex-1	18500	55723;55724;55725	chr2:178563814;178563813;178563812	chr2:179428541;179428540;179428539
Novex-2	18567	55924;55925;55926	chr2:178563814;178563813;178563812	chr2:179428541;179428540;179428539
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-87
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0933
• 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
Y/C	rs781246930	-2.344	0.999	D	0.851	0.894	0.933827315652	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
Y/C	rs781246930	-2.344	0.999	D	0.851	0.894	0.933827315652	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	5.65483E-05	0	None	0	0	None	0	0	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
Y/A	0.9981	likely_pathogenic	0.9977	pathogenic	-3.584	Highly Destabilizing	0.916	D	0.845	deleterious	None	None	None	None	N
Y/C	0.9863	likely_pathogenic	0.9824	pathogenic	-2.155	Highly Destabilizing	0.999	D	0.851	deleterious	D	0.687562268	None	None	N
Y/D	0.9938	likely_pathogenic	0.9921	pathogenic	-3.678	Highly Destabilizing	0.025	N	0.743	deleterious	D	0.687562268	None	None	N
Y/E	0.9989	likely_pathogenic	0.9987	pathogenic	-3.496	Highly Destabilizing	0.845	D	0.849	deleterious	None	None	None	None	N
Y/F	0.7266	likely_pathogenic	0.7091	pathogenic	-1.418	Destabilizing	0.981	D	0.721	prob.delet.	D	0.653475143	None	None	N
Y/G	0.9876	likely_pathogenic	0.9856	pathogenic	-3.977	Highly Destabilizing	0.975	D	0.851	deleterious	None	None	None	None	N
Y/H	0.9954	likely_pathogenic	0.9943	pathogenic	-2.357	Highly Destabilizing	0.994	D	0.792	deleterious	D	0.662024156	None	None	N
Y/I	0.9849	likely_pathogenic	0.9846	pathogenic	-2.27	Highly Destabilizing	0.987	D	0.811	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9989	pathogenic	-2.427	Highly Destabilizing	0.975	D	0.856	deleterious	None	None	None	None	N
Y/L	0.9701	likely_pathogenic	0.9671	pathogenic	-2.27	Highly Destabilizing	0.957	D	0.8	deleterious	None	None	None	None	N
Y/M	0.9914	likely_pathogenic	0.99	pathogenic	-1.988	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
Y/N	0.9723	likely_pathogenic	0.9643	pathogenic	-3.104	Highly Destabilizing	0.935	D	0.858	deleterious	D	0.687360463	None	None	N
Y/P	0.9993	likely_pathogenic	0.9992	pathogenic	-2.724	Highly Destabilizing	0.987	D	0.88	deleterious	None	None	None	None	N
Y/Q	0.9994	likely_pathogenic	0.9992	pathogenic	-2.941	Highly Destabilizing	0.987	D	0.816	deleterious	None	None	None	None	N
Y/R	0.9981	likely_pathogenic	0.9978	pathogenic	-1.96	Destabilizing	0.987	D	0.868	deleterious	None	None	None	None	N
Y/S	0.9932	likely_pathogenic	0.9915	pathogenic	-3.499	Highly Destabilizing	0.967	D	0.837	deleterious	D	0.687562268	None	None	N
Y/T	0.9971	likely_pathogenic	0.9965	pathogenic	-3.208	Highly Destabilizing	0.975	D	0.848	deleterious	None	None	None	None	N
Y/V	0.9672	likely_pathogenic	0.9669	pathogenic	-2.724	Highly Destabilizing	0.987	D	0.795	deleterious	None	None	None	None	N
Y/W	0.9693	likely_pathogenic	0.9677	pathogenic	-0.693	Destabilizing	0.999	D	0.784	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.