TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31496	94711;94712;94713	chr2:178547039;178547038;178547037	chr2:179411766;179411765;179411764
N2AB	29855	89788;89789;89790	chr2:178547039;178547038;178547037	chr2:179411766;179411765;179411764
N2A	28928	87007;87008;87009	chr2:178547039;178547038;178547037	chr2:179411766;179411765;179411764
N2B	22431	67516;67517;67518	chr2:178547039;178547038;178547037	chr2:179411766;179411765;179411764
Novex-1	22556	67891;67892;67893	chr2:178547039;178547038;178547037	chr2:179411766;179411765;179411764
Novex-2	22623	68092;68093;68094	chr2:178547039;178547038;178547037	chr2:179411766;179411765;179411764
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: Fn3-117
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.2561
• 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/K	rs769175534	-0.12	0.998	N	0.58	0.365	0.327686398923	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	3.27E-05	None	4.66E-05	2.67E-05	1.66113E-04
E/K	rs769175534	-0.12	0.998	N	0.58	0.365	0.327686398923	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs769175534	-0.12	0.998	N	0.58	0.365	0.327686398923	gnomAD-4.0.0	1.30175E-05	None	None	None	None	N	None	0	5.00183E-05	None	0	2.22806E-05	None	0	0	1.01747E-05	2.1964E-05	4.8043E-05
E/Q	None	None	1.0	N	0.603	0.253	0.412587454835	gnomAD-4.0.0	6.84448E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99782E-07	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	0.4904	ambiguous	0.4546	ambiguous	-0.429	Destabilizing	0.976	D	0.587	neutral	N	0.481115279	None	None	N
E/C	0.9813	likely_pathogenic	0.9771	pathogenic	-0.007	Destabilizing	1.0	D	0.726	deleterious	None	None	None	None	N
E/D	0.3061	likely_benign	0.2417	benign	-0.354	Destabilizing	0.988	D	0.565	neutral	N	0.457814345	None	None	N
E/F	0.967	likely_pathogenic	0.962	pathogenic	-0.335	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/G	0.6069	likely_pathogenic	0.5776	pathogenic	-0.616	Destabilizing	0.114	N	0.531	neutral	D	0.523308618	None	None	N
E/H	0.9108	likely_pathogenic	0.8916	pathogenic	-0.101	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
E/I	0.7827	likely_pathogenic	0.7712	pathogenic	0.028	Stabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
E/K	0.6543	likely_pathogenic	0.6128	pathogenic	0.38	Stabilizing	0.998	D	0.58	neutral	N	0.427686226	None	None	N
E/L	0.8053	likely_pathogenic	0.7844	pathogenic	0.028	Stabilizing	0.999	D	0.691	prob.delet.	None	None	None	None	N
E/M	0.8532	likely_pathogenic	0.8462	pathogenic	0.17	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/N	0.7872	likely_pathogenic	0.7345	pathogenic	0.04	Stabilizing	0.997	D	0.596	neutral	None	None	None	None	N
E/P	0.8071	likely_pathogenic	0.7516	pathogenic	-0.104	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
E/Q	0.4928	ambiguous	0.4571	ambiguous	0.064	Stabilizing	1.0	D	0.603	neutral	N	0.512091547	None	None	N
E/R	0.7745	likely_pathogenic	0.7446	pathogenic	0.551	Stabilizing	0.999	D	0.579	neutral	None	None	None	None	N
E/S	0.6657	likely_pathogenic	0.6245	pathogenic	-0.11	Destabilizing	0.982	D	0.578	neutral	None	None	None	None	N
E/T	0.7329	likely_pathogenic	0.6948	pathogenic	0.047	Stabilizing	0.997	D	0.563	neutral	None	None	None	None	N
E/V	0.5828	likely_pathogenic	0.5633	ambiguous	-0.104	Destabilizing	0.999	D	0.645	neutral	N	0.466595845	None	None	N
E/W	0.9912	likely_pathogenic	0.989	pathogenic	-0.177	Destabilizing	1.0	D	0.722	deleterious	None	None	None	None	N
E/Y	0.9396	likely_pathogenic	0.929	pathogenic	-0.086	Destabilizing	0.999	D	0.723	deleterious	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.