TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27297	82114;82115;82116	chr2:178564243;178564242;178564241	chr2:179428970;179428969;179428968
N2AB	25656	77191;77192;77193	chr2:178564243;178564242;178564241	chr2:179428970;179428969;179428968
N2A	24729	74410;74411;74412	chr2:178564243;178564242;178564241	chr2:179428970;179428969;179428968
N2B	18232	54919;54920;54921	chr2:178564243;178564242;178564241	chr2:179428970;179428969;179428968
Novex-1	18357	55294;55295;55296	chr2:178564243;178564242;178564241	chr2:179428970;179428969;179428968
Novex-2	18424	55495;55496;55497	chr2:178564243;178564242;178564241	chr2:179428970;179428969;179428968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-140
• Domain position: 20
• Structural Position: 33
• Q(SASA): 0.098
• 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
A/T	rs774451230	None	0.984	N	0.734	0.361	0.262662153117	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
A/T	rs774451230	None	0.984	N	0.734	0.361	0.262662153117	gnomAD-4.0.0	1.85972E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54283E-05	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	0.7034	likely_pathogenic	0.7324	pathogenic	-1.091	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
A/D	0.9868	likely_pathogenic	0.987	pathogenic	-1.262	Destabilizing	0.998	D	0.885	deleterious	N	0.502233426	None	None	N
A/E	0.9829	likely_pathogenic	0.9823	pathogenic	-1.261	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
A/F	0.8988	likely_pathogenic	0.8941	pathogenic	-1.037	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
A/G	0.2217	likely_benign	0.2471	benign	-1.326	Destabilizing	0.992	D	0.714	prob.delet.	N	0.483875681	None	None	N
A/H	0.9906	likely_pathogenic	0.9907	pathogenic	-1.371	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
A/I	0.7173	likely_pathogenic	0.7238	pathogenic	-0.356	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
A/K	0.9937	likely_pathogenic	0.993	pathogenic	-1.327	Destabilizing	0.998	D	0.838	deleterious	None	None	None	None	N
A/L	0.6418	likely_pathogenic	0.6441	pathogenic	-0.356	Destabilizing	0.997	D	0.771	deleterious	None	None	None	None	N
A/M	0.6222	likely_pathogenic	0.6088	pathogenic	-0.352	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/N	0.9664	likely_pathogenic	0.9681	pathogenic	-1.121	Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
A/P	0.9913	likely_pathogenic	0.9921	pathogenic	-0.537	Destabilizing	0.999	D	0.851	deleterious	N	0.484129171	None	None	N
A/Q	0.9792	likely_pathogenic	0.9783	pathogenic	-1.233	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
A/R	0.987	likely_pathogenic	0.986	pathogenic	-0.962	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
A/S	0.3335	likely_benign	0.3532	ambiguous	-1.524	Destabilizing	0.916	D	0.439	neutral	N	0.478849252	None	None	N
A/T	0.3411	ambiguous	0.3572	ambiguous	-1.41	Destabilizing	0.984	D	0.734	prob.delet.	N	0.455883152	None	None	N
A/V	0.3845	ambiguous	0.3872	ambiguous	-0.537	Destabilizing	0.996	D	0.778	deleterious	N	0.486893953	None	None	N
A/W	0.9914	likely_pathogenic	0.9904	pathogenic	-1.381	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
A/Y	0.9644	likely_pathogenic	0.9623	pathogenic	-0.973	Destabilizing	1.0	D	0.906	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.