TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32245	96958;96959;96960	chr2:178543240;178543239;178543238	chr2:179407967;179407966;179407965
N2AB	30604	92035;92036;92037	chr2:178543240;178543239;178543238	chr2:179407967;179407966;179407965
N2A	29677	89254;89255;89256	chr2:178543240;178543239;178543238	chr2:179407967;179407966;179407965
N2B	23180	69763;69764;69765	chr2:178543240;178543239;178543238	chr2:179407967;179407966;179407965
Novex-1	23305	70138;70139;70140	chr2:178543240;178543239;178543238	chr2:179407967;179407966;179407965
Novex-2	23372	70339;70340;70341	chr2:178543240;178543239;178543238	chr2:179407967;179407966;179407965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-123
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.6827
• 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
G/S	rs1559120718	None	0.986	N	0.554	0.326	0.363158594168	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65563E-04
G/S	rs1559120718	None	0.986	N	0.554	0.326	0.363158594168	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02389E-05

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
G/A	0.3217	likely_benign	0.2656	benign	-0.332	Destabilizing	0.976	D	0.509	neutral	N	0.499647899	None	None	N
G/C	0.519	ambiguous	0.4555	ambiguous	-0.973	Destabilizing	1.0	D	0.734	prob.delet.	D	0.526142984	None	None	N
G/D	0.3313	likely_benign	0.2739	benign	-0.782	Destabilizing	0.388	N	0.52	neutral	N	0.492199065	None	None	N
G/E	0.447	ambiguous	0.3919	ambiguous	-0.938	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
G/F	0.8422	likely_pathogenic	0.7914	pathogenic	-1.114	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
G/H	0.6114	likely_pathogenic	0.5531	ambiguous	-0.404	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
G/I	0.722	likely_pathogenic	0.6496	pathogenic	-0.596	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
G/K	0.6823	likely_pathogenic	0.6415	pathogenic	-0.779	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
G/L	0.7816	likely_pathogenic	0.7188	pathogenic	-0.596	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
G/M	0.787	likely_pathogenic	0.731	pathogenic	-0.726	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
G/N	0.3665	ambiguous	0.3026	benign	-0.445	Destabilizing	0.998	D	0.566	neutral	None	None	None	None	N
G/P	0.9374	likely_pathogenic	0.9181	pathogenic	-0.485	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
G/Q	0.5429	ambiguous	0.4943	ambiguous	-0.722	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
G/R	0.5627	ambiguous	0.516	ambiguous	-0.336	Destabilizing	0.999	D	0.701	prob.neutral	N	0.48172804	None	None	N
G/S	0.1724	likely_benign	0.1432	benign	-0.567	Destabilizing	0.986	D	0.554	neutral	N	0.517558869	None	None	N
G/T	0.3882	ambiguous	0.3237	benign	-0.667	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
G/V	0.5682	likely_pathogenic	0.4918	ambiguous	-0.485	Destabilizing	0.999	D	0.741	deleterious	N	0.47953922	None	None	N
G/W	0.7315	likely_pathogenic	0.6978	pathogenic	-1.202	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
G/Y	0.7535	likely_pathogenic	0.6874	pathogenic	-0.911	Destabilizing	1.0	D	0.714	prob.delet.	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.