TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8501	25726;25727;25728	chr2:178717233;178717232;178717231	chr2:179581960;179581959;179581958
N2AB	8184	24775;24776;24777	chr2:178717233;178717232;178717231	chr2:179581960;179581959;179581958
N2A	7257	21994;21995;21996	chr2:178717233;178717232;178717231	chr2:179581960;179581959;179581958
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-70
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.5936
• 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
N/K	rs758559820	0.453	0.388	N	0.178	0.087	0.115124310173	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	1.65782E-04
N/K	rs758559820	0.453	0.388	N	0.178	0.087	0.115124310173	gnomAD-4.0.0	5.47423E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.11557E-05	1.657E-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
N/A	0.6102	likely_pathogenic	0.6694	pathogenic	-0.675	Destabilizing	0.252	N	0.311	neutral	None	None	None	None	N
N/C	0.7428	likely_pathogenic	0.7721	pathogenic	0.155	Stabilizing	0.999	D	0.467	neutral	None	None	None	None	N
N/D	0.6202	likely_pathogenic	0.6458	pathogenic	0.311	Stabilizing	0.792	D	0.365	neutral	N	0.493571996	None	None	N
N/E	0.9178	likely_pathogenic	0.9269	pathogenic	0.346	Stabilizing	0.894	D	0.309	neutral	None	None	None	None	N
N/F	0.8524	likely_pathogenic	0.8785	pathogenic	-0.711	Destabilizing	0.999	D	0.447	neutral	None	None	None	None	N
N/G	0.6567	likely_pathogenic	0.7001	pathogenic	-0.936	Destabilizing	0.946	D	0.309	neutral	None	None	None	None	N
N/H	0.307	likely_benign	0.3294	benign	-0.678	Destabilizing	0.992	D	0.404	neutral	N	0.499401891	None	None	N
N/I	0.4883	ambiguous	0.562	ambiguous	-0.047	Destabilizing	0.992	D	0.439	neutral	N	0.50827209	None	None	N
N/K	0.8055	likely_pathogenic	0.8112	pathogenic	0.07	Stabilizing	0.388	N	0.178	neutral	N	0.477754395	None	None	N
N/L	0.5379	ambiguous	0.592	pathogenic	-0.047	Destabilizing	0.979	D	0.419	neutral	None	None	None	None	N
N/M	0.7012	likely_pathogenic	0.7497	pathogenic	0.254	Stabilizing	0.999	D	0.387	neutral	None	None	None	None	N
N/P	0.8096	likely_pathogenic	0.826	pathogenic	-0.227	Destabilizing	0.973	D	0.395	neutral	None	None	None	None	N
N/Q	0.7566	likely_pathogenic	0.7771	pathogenic	-0.458	Destabilizing	0.679	D	0.227	neutral	None	None	None	None	N
N/R	0.7894	likely_pathogenic	0.794	pathogenic	0.093	Stabilizing	0.969	D	0.373	neutral	None	None	None	None	N
N/S	0.175	likely_benign	0.2024	benign	-0.467	Destabilizing	0.059	N	0.106	neutral	N	0.487107384	None	None	N
N/T	0.3752	ambiguous	0.4509	ambiguous	-0.247	Destabilizing	0.747	D	0.313	neutral	N	0.510714962	None	None	N
N/V	0.5705	likely_pathogenic	0.6352	pathogenic	-0.227	Destabilizing	0.933	D	0.425	neutral	None	None	None	None	N
N/W	0.9547	likely_pathogenic	0.9608	pathogenic	-0.527	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	N
N/Y	0.433	ambiguous	0.4698	ambiguous	-0.308	Destabilizing	0.999	D	0.391	neutral	N	0.464161584	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.