TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29452	88579;88580;88581	chr2:178555105;178555104;178555103	chr2:179419832;179419831;179419830
N2AB	27811	83656;83657;83658	chr2:178555105;178555104;178555103	chr2:179419832;179419831;179419830
N2A	26884	80875;80876;80877	chr2:178555105;178555104;178555103	chr2:179419832;179419831;179419830
N2B	20387	61384;61385;61386	chr2:178555105;178555104;178555103	chr2:179419832;179419831;179419830
Novex-1	20512	61759;61760;61761	chr2:178555105;178555104;178555103	chr2:179419832;179419831;179419830
Novex-2	20579	61960;61961;61962	chr2:178555105;178555104;178555103	chr2:179419832;179419831;179419830
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-146
• Domain position: 9
• Structural Position: 16
• Q(SASA): 0.3558
• Predicted PPI site: I

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/H	rs763288364	-0.137	0.028	N	0.338	0.225	0.301455362545	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	2.23189E-04	None	0	None	0	0	0
Y/H	rs763288364	-0.137	0.028	N	0.338	0.225	0.301455362545	gnomAD-4.0.0	1.4322E-05	None	None	None	None	I	None	0	0	None	0	2.49709E-04	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	0.6917	likely_pathogenic	0.7194	pathogenic	-1.868	Destabilizing	0.915	D	0.377	neutral	None	None	None	None	I
Y/C	0.1409	likely_benign	0.1826	benign	-0.875	Destabilizing	0.997	D	0.44	neutral	N	0.392875511	None	None	I
Y/D	0.7748	likely_pathogenic	0.7874	pathogenic	-0.517	Destabilizing	0.966	D	0.475	neutral	N	0.430663108	None	None	I
Y/E	0.8471	likely_pathogenic	0.8612	pathogenic	-0.409	Destabilizing	0.949	D	0.442	neutral	None	None	None	None	I
Y/F	0.1116	likely_benign	0.1119	benign	-0.557	Destabilizing	0.012	N	0.168	neutral	N	0.363342038	None	None	I
Y/G	0.676	likely_pathogenic	0.7229	pathogenic	-2.192	Highly Destabilizing	0.974	D	0.482	neutral	None	None	None	None	I
Y/H	0.2946	likely_benign	0.3202	benign	-0.585	Destabilizing	0.028	N	0.338	neutral	N	0.412077347	None	None	I
Y/I	0.5082	ambiguous	0.5327	ambiguous	-0.894	Destabilizing	0.142	N	0.235	neutral	None	None	None	None	I
Y/K	0.7712	likely_pathogenic	0.7966	pathogenic	-1.06	Destabilizing	0.974	D	0.458	neutral	None	None	None	None	I
Y/L	0.5199	ambiguous	0.5407	ambiguous	-0.894	Destabilizing	0.525	D	0.343	neutral	None	None	None	None	I
Y/M	0.6823	likely_pathogenic	0.6963	pathogenic	-0.731	Destabilizing	0.974	D	0.434	neutral	None	None	None	None	I
Y/N	0.5054	ambiguous	0.5296	ambiguous	-1.542	Destabilizing	0.934	D	0.439	neutral	N	0.43048975	None	None	I
Y/P	0.9795	likely_pathogenic	0.9813	pathogenic	-1.213	Destabilizing	0.991	D	0.49	neutral	None	None	None	None	I
Y/Q	0.674	likely_pathogenic	0.712	pathogenic	-1.361	Destabilizing	0.974	D	0.433	neutral	None	None	None	None	I
Y/R	0.6655	likely_pathogenic	0.6999	pathogenic	-0.772	Destabilizing	0.974	D	0.452	neutral	None	None	None	None	I
Y/S	0.5261	ambiguous	0.5612	ambiguous	-2.053	Highly Destabilizing	0.966	D	0.435	neutral	N	0.430143033	None	None	I
Y/T	0.6808	likely_pathogenic	0.7044	pathogenic	-1.844	Destabilizing	0.974	D	0.446	neutral	None	None	None	None	I
Y/V	0.4108	ambiguous	0.4334	ambiguous	-1.213	Destabilizing	0.728	D	0.322	neutral	None	None	None	None	I
Y/W	0.5369	ambiguous	0.5591	ambiguous	-0.182	Destabilizing	0.998	D	0.447	neutral	None	None	None	None	I

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.