TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8931	27016;27017;27018	chr2:178713343;178713342;178713341	chr2:179578070;179578069;179578068
N2AB	8614	26065;26066;26067	chr2:178713343;178713342;178713341	chr2:179578070;179578069;179578068
N2A	7687	23284;23285;23286	chr2:178713343;178713342;178713341	chr2:179578070;179578069;179578068
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-75
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.706
• 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
K/I	rs759670367	0.688	0.001	N	0.399	0.164	0.471539375507	gnomAD-2.1.1	5.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.49E-05	0
K/I	rs759670367	0.688	0.001	N	0.399	0.164	0.471539375507	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/I	rs759670367	0.688	0.001	N	0.399	0.164	0.471539375507	gnomAD-4.0.0	3.85826E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.2282E-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
K/A	0.3971	ambiguous	0.4878	ambiguous	-0.424	Destabilizing	0.035	N	0.498	neutral	None	None	None	None	N
K/C	0.7048	likely_pathogenic	0.7529	pathogenic	-0.482	Destabilizing	0.935	D	0.612	neutral	None	None	None	None	N
K/D	0.6687	likely_pathogenic	0.7521	pathogenic	0.286	Stabilizing	0.38	N	0.527	neutral	None	None	None	None	N
K/E	0.245	likely_benign	0.3199	benign	0.381	Stabilizing	0.062	N	0.517	neutral	N	0.491866283	None	None	N
K/F	0.6885	likely_pathogenic	0.7778	pathogenic	-0.189	Destabilizing	0.38	N	0.611	neutral	None	None	None	None	N
K/G	0.4414	ambiguous	0.5158	ambiguous	-0.748	Destabilizing	0.149	N	0.555	neutral	None	None	None	None	N
K/H	0.3044	likely_benign	0.3583	ambiguous	-0.917	Destabilizing	0.824	D	0.561	neutral	None	None	None	None	N
K/I	0.3456	ambiguous	0.4442	ambiguous	0.393	Stabilizing	0.001	N	0.399	neutral	N	0.494695685	None	None	N
K/L	0.3332	likely_benign	0.4121	ambiguous	0.393	Stabilizing	0.029	N	0.52	neutral	None	None	None	None	N
K/M	0.2314	likely_benign	0.2882	benign	0.107	Stabilizing	0.38	N	0.56	neutral	None	None	None	None	N
K/N	0.4454	ambiguous	0.5433	ambiguous	-0.151	Destabilizing	0.117	N	0.51	neutral	N	0.48922841	None	None	N
K/P	0.4754	ambiguous	0.5619	ambiguous	0.151	Stabilizing	0.555	D	0.573	neutral	None	None	None	None	N
K/Q	0.1432	likely_benign	0.1685	benign	-0.206	Destabilizing	0.317	N	0.551	neutral	N	0.496080024	None	None	N
K/R	0.0774	likely_benign	0.0787	benign	-0.28	Destabilizing	None	N	0.163	neutral	N	0.515820578	None	None	N
K/S	0.4685	ambiguous	0.568	pathogenic	-0.821	Destabilizing	0.007	N	0.223	neutral	None	None	None	None	N
K/T	0.2357	likely_benign	0.3079	benign	-0.525	Destabilizing	0.062	N	0.533	neutral	N	0.521746472	None	None	N
K/V	0.351	ambiguous	0.4352	ambiguous	0.151	Stabilizing	0.029	N	0.531	neutral	None	None	None	None	N
K/W	0.6472	likely_pathogenic	0.7139	pathogenic	-0.078	Destabilizing	0.935	D	0.688	prob.neutral	None	None	None	None	N
K/Y	0.5355	ambiguous	0.6165	pathogenic	0.209	Stabilizing	0.555	D	0.61	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.