TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7635	23128;23129;23130	chr2:178721116;178721115;178721114	chr2:179585843;179585842;179585841
N2AB	7318	22177;22178;22179	chr2:178721116;178721115;178721114	chr2:179585843;179585842;179585841
N2A	6391	19396;19397;19398	chr2:178721116;178721115;178721114	chr2:179585843;179585842;179585841
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-61
• Domain position: 28
• Structural Position: 41
• Q(SASA): 0.4937
• 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
S/F	rs1268436239	-0.833	0.992	N	0.586	0.399	0.817150913411	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
S/F	rs1268436239	-0.833	0.992	N	0.586	0.399	0.817150913411	gnomAD-4.0.0	2.05336E-06	None	None	None	None	I	None	0	0	None	0	2.51953E-05	None	0	0	1.79957E-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
S/A	0.1943	likely_benign	0.1528	benign	-0.06	Destabilizing	0.065	N	0.301	neutral	N	0.486186536	None	None	I
S/C	0.4314	ambiguous	0.3136	benign	-0.46	Destabilizing	0.997	D	0.451	neutral	N	0.495051307	None	None	I
S/D	0.7841	likely_pathogenic	0.7541	pathogenic	-0.046	Destabilizing	0.857	D	0.344	neutral	None	None	None	None	I
S/E	0.8578	likely_pathogenic	0.8018	pathogenic	-0.148	Destabilizing	0.893	D	0.352	neutral	None	None	None	None	I
S/F	0.2573	likely_benign	0.2078	benign	-0.806	Destabilizing	0.992	D	0.586	neutral	N	0.521573114	None	None	I
S/G	0.3088	likely_benign	0.3016	benign	-0.101	Destabilizing	0.821	D	0.319	neutral	None	None	None	None	I
S/H	0.6306	likely_pathogenic	0.5348	ambiguous	-0.357	Destabilizing	0.999	D	0.453	neutral	None	None	None	None	I
S/I	0.3122	likely_benign	0.2308	benign	-0.083	Destabilizing	0.987	D	0.581	neutral	None	None	None	None	I
S/K	0.948	likely_pathogenic	0.911	pathogenic	-0.395	Destabilizing	0.957	D	0.345	neutral	None	None	None	None	I
S/L	0.1569	likely_benign	0.1355	benign	-0.083	Destabilizing	0.918	D	0.551	neutral	None	None	None	None	I
S/M	0.3095	likely_benign	0.2574	benign	-0.214	Destabilizing	0.998	D	0.455	neutral	None	None	None	None	I
S/N	0.3601	ambiguous	0.2942	benign	-0.179	Destabilizing	0.413	N	0.389	neutral	None	None	None	None	I
S/P	0.9138	likely_pathogenic	0.9198	pathogenic	-0.051	Destabilizing	0.014	N	0.253	neutral	N	0.514965987	None	None	I
S/Q	0.82	likely_pathogenic	0.7306	pathogenic	-0.384	Destabilizing	0.994	D	0.421	neutral	None	None	None	None	I
S/R	0.9317	likely_pathogenic	0.8857	pathogenic	-0.121	Destabilizing	0.994	D	0.457	neutral	None	None	None	None	I
S/T	0.1089	likely_benign	0.1071	benign	-0.274	Destabilizing	0.001	N	0.155	neutral	N	0.455905482	None	None	I
S/V	0.3469	ambiguous	0.2544	benign	-0.051	Destabilizing	0.808	D	0.551	neutral	None	None	None	None	I
S/W	0.5466	ambiguous	0.4976	ambiguous	-0.923	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
S/Y	0.2937	likely_benign	0.2399	benign	-0.588	Destabilizing	0.997	D	0.585	neutral	N	0.509451966	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.