TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33462	100609;100610;100611	chr2:178536363;178536362;178536361	chr2:179401090;179401089;179401088
N2AB	31821	95686;95687;95688	chr2:178536363;178536362;178536361	chr2:179401090;179401089;179401088
N2A	30894	92905;92906;92907	chr2:178536363;178536362;178536361	chr2:179401090;179401089;179401088
N2B	24397	73414;73415;73416	chr2:178536363;178536362;178536361	chr2:179401090;179401089;179401088
Novex-1	24522	73789;73790;73791	chr2:178536363;178536362;178536361	chr2:179401090;179401089;179401088
Novex-2	24589	73990;73991;73992	chr2:178536363;178536362;178536361	chr2:179401090;179401089;179401088
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: Fn3-131
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.2868
• 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/A	None	None	0.999	N	0.687	0.581	0.418718287753	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	0	0
E/K	rs748104690	-0.719	0.999	N	0.601	0.385	0.385417323374	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	1.98345E-04	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs748104690	-0.719	0.999	N	0.601	0.385	0.385417323374	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	0	3.92619E-04	0	0	0	None	0	0	0	0	0
E/K	rs748104690	-0.719	0.999	N	0.601	0.385	0.385417323374	gnomAD-4.0.0	1.61127E-05	None	None	None	None	N	None	0	3.334E-04	None	0	0	None	0	0	0	6.58834E-05	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	0.1783	likely_benign	0.1671	benign	-0.775	Destabilizing	0.999	D	0.687	prob.neutral	N	0.479650898	None	None	N
E/C	0.8719	likely_pathogenic	0.8458	pathogenic	-0.63	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/D	0.2684	likely_benign	0.224	benign	-1.537	Destabilizing	0.999	D	0.493	neutral	N	0.48473978	None	None	N
E/F	0.9061	likely_pathogenic	0.885	pathogenic	-0.12	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/G	0.2896	likely_benign	0.3147	benign	-1.214	Destabilizing	1.0	D	0.739	prob.delet.	N	0.487488484	None	None	N
E/H	0.7381	likely_pathogenic	0.6905	pathogenic	-0.571	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/I	0.4901	ambiguous	0.4037	ambiguous	0.45	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/K	0.3911	ambiguous	0.3913	ambiguous	-1.182	Destabilizing	0.999	D	0.601	neutral	N	0.468241686	None	None	N
E/L	0.6067	likely_pathogenic	0.546	ambiguous	0.45	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/M	0.6518	likely_pathogenic	0.5923	pathogenic	0.966	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/N	0.4744	ambiguous	0.4213	ambiguous	-1.611	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/P	0.5953	likely_pathogenic	0.6185	pathogenic	0.063	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Q	0.1976	likely_benign	0.1855	benign	-1.361	Destabilizing	1.0	D	0.643	neutral	N	0.520463101	None	None	N
E/R	0.544	ambiguous	0.5462	ambiguous	-0.958	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/S	0.2574	likely_benign	0.2416	benign	-2.057	Highly Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
E/T	0.2838	likely_benign	0.236	benign	-1.683	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/V	0.3006	likely_benign	0.2443	benign	0.063	Stabilizing	1.0	D	0.771	deleterious	N	0.476385668	None	None	N
E/W	0.968	likely_pathogenic	0.9645	pathogenic	-0.035	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/Y	0.8586	likely_pathogenic	0.8358	pathogenic	0.079	Stabilizing	1.0	D	0.773	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.