TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23996	72211;72212;72213	chr2:178574146;178574145;178574144	chr2:179438873;179438872;179438871
N2AB	22355	67288;67289;67290	chr2:178574146;178574145;178574144	chr2:179438873;179438872;179438871
N2A	21428	64507;64508;64509	chr2:178574146;178574145;178574144	chr2:179438873;179438872;179438871
N2B	14931	45016;45017;45018	chr2:178574146;178574145;178574144	chr2:179438873;179438872;179438871
Novex-1	15056	45391;45392;45393	chr2:178574146;178574145;178574144	chr2:179438873;179438872;179438871
Novex-2	15123	45592;45593;45594	chr2:178574146;178574145;178574144	chr2:179438873;179438872;179438871
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: Fn3-62
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.1398
• 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/A	rs769265681	-1.241	0.999	N	0.655	0.582	0.484691182572	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/A	rs769265681	-1.241	0.999	N	0.655	0.582	0.484691182572	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8591E-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
E/A	0.3768	ambiguous	0.4171	ambiguous	-0.52	Destabilizing	0.999	D	0.655	neutral	N	0.485095401	None	None	N
E/C	0.9232	likely_pathogenic	0.9231	pathogenic	0.118	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/D	0.6749	likely_pathogenic	0.7203	pathogenic	-1.351	Destabilizing	0.999	D	0.547	neutral	N	0.520407173	None	None	N
E/F	0.9553	likely_pathogenic	0.9559	pathogenic	-0.041	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/G	0.6923	likely_pathogenic	0.7233	pathogenic	-0.981	Destabilizing	1.0	D	0.703	prob.neutral	N	0.517380345	None	None	N
E/H	0.8663	likely_pathogenic	0.8727	pathogenic	-0.077	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/I	0.6763	likely_pathogenic	0.6712	pathogenic	0.788	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/K	0.6057	likely_pathogenic	0.6294	pathogenic	-0.423	Destabilizing	0.999	D	0.599	neutral	D	0.524138125	None	None	N
E/L	0.8058	likely_pathogenic	0.8034	pathogenic	0.788	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/M	0.715	likely_pathogenic	0.7221	pathogenic	1.414	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.7909	likely_pathogenic	0.8191	pathogenic	-0.918	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/P	0.9972	likely_pathogenic	0.9972	pathogenic	0.371	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/Q	0.2203	likely_benign	0.2246	benign	-0.557	Destabilizing	1.0	D	0.668	neutral	N	0.514614564	None	None	N
E/R	0.7246	likely_pathogenic	0.7369	pathogenic	-0.45	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/S	0.4998	ambiguous	0.5404	ambiguous	-1.5	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
E/T	0.5734	likely_pathogenic	0.6095	pathogenic	-1.056	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/V	0.4762	ambiguous	0.4831	ambiguous	0.371	Stabilizing	1.0	D	0.697	prob.neutral	N	0.515961359	None	None	N
E/W	0.9907	likely_pathogenic	0.9912	pathogenic	-0.133	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/Y	0.9315	likely_pathogenic	0.9323	pathogenic	0.214	Stabilizing	1.0	D	0.738	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.