TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20716	62371;62372;62373	chr2:178589579;178589578;178589577	chr2:179454306;179454305;179454304
N2AB	19075	57448;57449;57450	chr2:178589579;178589578;178589577	chr2:179454306;179454305;179454304
N2A	18148	54667;54668;54669	chr2:178589579;178589578;178589577	chr2:179454306;179454305;179454304
N2B	11651	35176;35177;35178	chr2:178589579;178589578;178589577	chr2:179454306;179454305;179454304
Novex-1	11776	35551;35552;35553	chr2:178589579;178589578;178589577	chr2:179454306;179454305;179454304
Novex-2	11843	35752;35753;35754	chr2:178589579;178589578;178589577	chr2:179454306;179454305;179454304
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: Fn3-38
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.5884
• 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	rs794729243	None	0.989	N	0.583	0.425	0.417460480802	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/A	rs794729243	None	0.989	N	0.583	0.425	0.417460480802	gnomAD-4.0.0	1.85953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69546E-06	0	1.60128E-05
E/K	None	None	0.978	N	0.572	0.336	0.359357374593	gnomAD-4.0.0	5.47496E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19673E-06	0	0
E/Q	rs548071435	-0.373	0.889	N	0.276	0.158	0.304760801415	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
E/Q	rs548071435	-0.373	0.889	N	0.276	0.158	0.304760801415	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/Q	rs548071435	-0.373	0.889	N	0.276	0.158	0.304760801415	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
E/Q	rs548071435	-0.373	0.889	N	0.276	0.158	0.304760801415	gnomAD-4.0.0	2.47921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39097E-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
E/A	0.3645	ambiguous	0.5242	ambiguous	-0.718	Destabilizing	0.989	D	0.583	neutral	N	0.502317271	None	None	N
E/C	0.8993	likely_pathogenic	0.9509	pathogenic	-0.395	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/D	0.2326	likely_benign	0.3495	ambiguous	-0.793	Destabilizing	0.217	N	0.289	neutral	N	0.472240931	None	None	N
E/F	0.8417	likely_pathogenic	0.9252	pathogenic	-0.202	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/G	0.4833	ambiguous	0.6031	pathogenic	-1.021	Destabilizing	0.994	D	0.579	neutral	N	0.466925013	None	None	N
E/H	0.6686	likely_pathogenic	0.797	pathogenic	-0.159	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
E/I	0.3698	ambiguous	0.5681	pathogenic	0.087	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/K	0.3872	ambiguous	0.5673	pathogenic	-0.198	Destabilizing	0.978	D	0.572	neutral	N	0.478920336	None	None	N
E/L	0.5259	ambiguous	0.7038	pathogenic	0.087	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
E/M	0.5487	ambiguous	0.7367	pathogenic	0.274	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/N	0.4834	ambiguous	0.67	pathogenic	-0.702	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	N
E/P	0.9872	likely_pathogenic	0.9883	pathogenic	-0.16	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/Q	0.2007	likely_benign	0.2834	benign	-0.62	Destabilizing	0.889	D	0.276	neutral	N	0.472994441	None	None	N
E/R	0.5925	likely_pathogenic	0.7273	pathogenic	0.164	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
E/S	0.4132	ambiguous	0.5597	ambiguous	-0.925	Destabilizing	0.992	D	0.584	neutral	None	None	None	None	N
E/T	0.3542	ambiguous	0.5276	ambiguous	-0.677	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
E/V	0.2306	likely_benign	0.3502	ambiguous	-0.16	Destabilizing	0.998	D	0.669	neutral	N	0.430859817	None	None	N
E/W	0.9597	likely_pathogenic	0.9816	pathogenic	0.082	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/Y	0.7944	likely_pathogenic	0.8957	pathogenic	0.067	Stabilizing	1.0	D	0.661	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.