TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32271	97036;97037;97038	chr2:178543162;178543161;178543160	chr2:179407889;179407888;179407887
N2AB	30630	92113;92114;92115	chr2:178543162;178543161;178543160	chr2:179407889;179407888;179407887
N2A	29703	89332;89333;89334	chr2:178543162;178543161;178543160	chr2:179407889;179407888;179407887
N2B	23206	69841;69842;69843	chr2:178543162;178543161;178543160	chr2:179407889;179407888;179407887
Novex-1	23331	70216;70217;70218	chr2:178543162;178543161;178543160	chr2:179407889;179407888;179407887
Novex-2	23398	70417;70418;70419	chr2:178543162;178543161;178543160	chr2:179407889;179407888;179407887
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: Fn3-123
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1625
• 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/G	rs1559120065	None	0.994	N	0.564	0.433	0.438806408302	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	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
E/A	0.3228	likely_benign	0.2854	benign	-0.807	Destabilizing	0.98	D	0.532	neutral	N	0.456064906	None	None	N
E/C	0.9076	likely_pathogenic	0.8918	pathogenic	-0.43	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/D	0.2173	likely_benign	0.1914	benign	-1.15	Destabilizing	0.004	N	0.174	neutral	N	0.478635121	None	None	N
E/F	0.8799	likely_pathogenic	0.8506	pathogenic	-0.218	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/G	0.2782	likely_benign	0.2564	benign	-1.18	Destabilizing	0.994	D	0.564	neutral	N	0.487331962	None	None	N
E/H	0.6623	likely_pathogenic	0.6364	pathogenic	-0.464	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
E/I	0.7034	likely_pathogenic	0.6421	pathogenic	0.21	Stabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
E/K	0.3388	likely_benign	0.3303	benign	-0.56	Destabilizing	0.989	D	0.499	neutral	N	0.453718034	None	None	N
E/L	0.682	likely_pathogenic	0.6146	pathogenic	0.21	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
E/M	0.6548	likely_pathogenic	0.6078	pathogenic	0.634	Stabilizing	0.997	D	0.675	neutral	None	None	None	None	N
E/N	0.4529	ambiguous	0.404	ambiguous	-1.067	Destabilizing	0.978	D	0.617	neutral	None	None	None	None	N
E/P	0.9702	likely_pathogenic	0.9685	pathogenic	-0.107	Destabilizing	0.989	D	0.647	neutral	None	None	None	None	N
E/Q	0.1847	likely_benign	0.1807	benign	-0.923	Destabilizing	0.996	D	0.636	neutral	N	0.440770167	None	None	N
E/R	0.4907	ambiguous	0.4801	ambiguous	-0.255	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
E/S	0.3145	likely_benign	0.2758	benign	-1.369	Destabilizing	0.969	D	0.497	neutral	None	None	None	None	N
E/T	0.453	ambiguous	0.4093	ambiguous	-1.058	Destabilizing	0.997	D	0.611	neutral	None	None	None	None	N
E/V	0.4755	ambiguous	0.4242	ambiguous	-0.107	Destabilizing	0.997	D	0.656	neutral	N	0.464839105	None	None	N
E/W	0.9581	likely_pathogenic	0.9535	pathogenic	0.04	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/Y	0.7934	likely_pathogenic	0.7634	pathogenic	0.04	Stabilizing	1.0	D	0.687	prob.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.