TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13954	42085;42086;42087	chr2:178635464;178635463;178635462	chr2:179500191;179500190;179500189
N2AB	12313	37162;37163;37164	chr2:178635464;178635463;178635462	chr2:179500191;179500190;179500189
N2A	11386	34381;34382;34383	chr2:178635464;178635463;178635462	chr2:179500191;179500190;179500189
N2B	4889	14890;14891;14892	chr2:178635464;178635463;178635462	chr2:179500191;179500190;179500189
Novex-1	5014	15265;15266;15267	chr2:178635464;178635463;178635462	chr2:179500191;179500190;179500189
Novex-2	5081	15466;15467;15468	chr2:178635464;178635463;178635462	chr2:179500191;179500190;179500189
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: Ig-89
• Domain position: 79
• Structural Position: 164
• Q(SASA): 0.1855
• 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	None	None	0.004	D	0.409	0.311	0.37568098594	gnomAD-4.0.0	3.21484E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.76671E-06	0	0
Y/H	None	None	0.924	D	0.465	0.286	0.39724302092	gnomAD-4.0.0	2.74832E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	3.47464E-04	1.80369E-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
Y/A	0.9451	likely_pathogenic	0.903	pathogenic	-2.608	Highly Destabilizing	0.134	N	0.448	neutral	None	None	None	None	N
Y/C	0.6539	likely_pathogenic	0.5304	ambiguous	-1.426	Destabilizing	0.004	N	0.409	neutral	D	0.562686496	None	None	N
Y/D	0.965	likely_pathogenic	0.9423	pathogenic	-2.363	Highly Destabilizing	0.664	D	0.621	neutral	D	0.561263881	None	None	N
Y/E	0.9805	likely_pathogenic	0.9621	pathogenic	-2.218	Highly Destabilizing	0.724	D	0.571	neutral	None	None	None	None	N
Y/F	0.2142	likely_benign	0.1614	benign	-0.965	Destabilizing	0.534	D	0.468	neutral	D	0.556818088	None	None	N
Y/G	0.943	likely_pathogenic	0.9091	pathogenic	-2.965	Highly Destabilizing	0.428	N	0.563	neutral	None	None	None	None	N
Y/H	0.7216	likely_pathogenic	0.58	pathogenic	-1.388	Destabilizing	0.924	D	0.465	neutral	D	0.561263881	None	None	N
Y/I	0.8149	likely_pathogenic	0.7176	pathogenic	-1.464	Destabilizing	0.272	N	0.411	neutral	None	None	None	None	N
Y/K	0.9751	likely_pathogenic	0.9517	pathogenic	-1.991	Destabilizing	0.724	D	0.569	neutral	None	None	None	None	N
Y/L	0.787	likely_pathogenic	0.7194	pathogenic	-1.464	Destabilizing	0.134	N	0.474	neutral	None	None	None	None	N
Y/M	0.9	likely_pathogenic	0.8383	pathogenic	-1.12	Destabilizing	0.842	D	0.425	neutral	None	None	None	None	N
Y/N	0.7942	likely_pathogenic	0.6684	pathogenic	-2.602	Highly Destabilizing	0.664	D	0.569	neutral	D	0.561263881	None	None	N
Y/P	0.9942	likely_pathogenic	0.9908	pathogenic	-1.85	Destabilizing	0.842	D	0.615	neutral	None	None	None	None	N
Y/Q	0.9523	likely_pathogenic	0.9057	pathogenic	-2.431	Highly Destabilizing	0.842	D	0.445	neutral	None	None	None	None	N
Y/R	0.9442	likely_pathogenic	0.9042	pathogenic	-1.632	Destabilizing	0.842	D	0.559	neutral	None	None	None	None	N
Y/S	0.8062	likely_pathogenic	0.6798	pathogenic	-2.964	Highly Destabilizing	0.022	N	0.41	neutral	N	0.501570456	None	None	N
Y/T	0.9188	likely_pathogenic	0.8402	pathogenic	-2.718	Highly Destabilizing	0.272	N	0.492	neutral	None	None	None	None	N
Y/V	0.7611	likely_pathogenic	0.6555	pathogenic	-1.85	Destabilizing	0.002	N	0.287	neutral	None	None	None	None	N
Y/W	0.7348	likely_pathogenic	0.692	pathogenic	-0.455	Destabilizing	0.984	D	0.478	neutral	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.