TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24077	72454;72455;72456	chr2:178573903;178573902;178573901	chr2:179438630;179438629;179438628
N2AB	22436	67531;67532;67533	chr2:178573903;178573902;178573901	chr2:179438630;179438629;179438628
N2A	21509	64750;64751;64752	chr2:178573903;178573902;178573901	chr2:179438630;179438629;179438628
N2B	15012	45259;45260;45261	chr2:178573903;178573902;178573901	chr2:179438630;179438629;179438628
Novex-1	15137	45634;45635;45636	chr2:178573903;178573902;178573901	chr2:179438630;179438629;179438628
Novex-2	15204	45835;45836;45837	chr2:178573903;178573902;178573901	chr2:179438630;179438629;179438628
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-131
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.4216
• 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
E/Q	None	None	1.0	N	0.555	0.3	0.357724736475	gnomAD-4.0.0	6.85309E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00782E-07	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
E/A	0.2562	likely_benign	0.258	benign	-0.919	Destabilizing	0.999	D	0.643	neutral	N	0.493201201	None	None	N
E/C	0.8973	likely_pathogenic	0.8879	pathogenic	-0.419	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/D	0.1732	likely_benign	0.1565	benign	-1.064	Destabilizing	0.999	D	0.429	neutral	D	0.534520982	None	None	N
E/F	0.8298	likely_pathogenic	0.8275	pathogenic	-0.526	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
E/G	0.3222	likely_benign	0.3235	benign	-1.267	Destabilizing	1.0	D	0.675	prob.neutral	N	0.49159504	None	None	N
E/H	0.5693	likely_pathogenic	0.538	ambiguous	-0.831	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
E/I	0.4346	ambiguous	0.4389	ambiguous	0.023	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/K	0.3491	ambiguous	0.3489	ambiguous	-0.502	Destabilizing	0.999	D	0.565	neutral	N	0.505600797	None	None	N
E/L	0.5142	ambiguous	0.5292	ambiguous	0.023	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/M	0.548	ambiguous	0.5697	pathogenic	0.506	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/N	0.3687	ambiguous	0.3679	ambiguous	-0.952	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/P	0.9683	likely_pathogenic	0.9599	pathogenic	-0.27	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/Q	0.1782	likely_benign	0.1798	benign	-0.836	Destabilizing	1.0	D	0.555	neutral	N	0.491460851	None	None	N
E/R	0.4823	ambiguous	0.4546	ambiguous	-0.327	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/S	0.2982	likely_benign	0.2954	benign	-1.259	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
E/T	0.2929	likely_benign	0.2866	benign	-0.965	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/V	0.2678	likely_benign	0.2774	benign	-0.27	Destabilizing	1.0	D	0.742	deleterious	D	0.529403163	None	None	N
E/W	0.9352	likely_pathogenic	0.9268	pathogenic	-0.296	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/Y	0.7546	likely_pathogenic	0.7284	pathogenic	-0.269	Destabilizing	1.0	D	0.717	prob.delet.	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.