TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8043	24352;24353;24354	chr2:178719263;178719262;178719261	chr2:179583990;179583989;179583988
N2AB	7726	23401;23402;23403	chr2:178719263;178719262;178719261	chr2:179583990;179583989;179583988
N2A	6799	20620;20621;20622	chr2:178719263;178719262;178719261	chr2:179583990;179583989;179583988
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: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-65
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2243
• 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/S	rs1462695230	-0.838	None	N	0.244	0.093	0.0986583533028	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs1462695230	-0.838	None	N	0.244	0.093	0.0986583533028	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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
N/A	0.1389	likely_benign	0.142	benign	-0.825	Destabilizing	0.004	N	0.451	neutral	None	None	None	None	N
N/C	0.2069	likely_benign	0.2148	benign	-0.341	Destabilizing	0.245	N	0.555	neutral	None	None	None	None	N
N/D	0.118	likely_benign	0.1217	benign	-1.462	Destabilizing	0.007	N	0.456	neutral	N	0.478704984	None	None	N
N/E	0.1924	likely_benign	0.1855	benign	-1.372	Destabilizing	0.009	N	0.412	neutral	None	None	None	None	N
N/F	0.2827	likely_benign	0.2951	benign	-0.899	Destabilizing	0.044	N	0.618	neutral	None	None	None	None	N
N/G	0.2128	likely_benign	0.2175	benign	-1.113	Destabilizing	0.004	N	0.398	neutral	None	None	None	None	N
N/H	0.0612	likely_benign	0.0619	benign	-0.923	Destabilizing	None	N	0.29	neutral	N	0.443957692	None	None	N
N/I	0.1237	likely_benign	0.1244	benign	-0.108	Destabilizing	None	N	0.491	neutral	N	0.409978405	None	None	N
N/K	0.1332	likely_benign	0.1141	benign	-0.194	Destabilizing	None	N	0.229	neutral	N	0.407804891	None	None	N
N/L	0.1322	likely_benign	0.131	benign	-0.108	Destabilizing	0.004	N	0.457	neutral	None	None	None	None	N
N/M	0.2011	likely_benign	0.1964	benign	0.431	Stabilizing	0.245	N	0.535	neutral	None	None	None	None	N
N/P	0.6233	likely_pathogenic	0.5767	pathogenic	-0.319	Destabilizing	0.044	N	0.571	neutral	None	None	None	None	N
N/Q	0.1504	likely_benign	0.1439	benign	-1.154	Destabilizing	0.044	N	0.485	neutral	None	None	None	None	N
N/R	0.1366	likely_benign	0.1242	benign	-0.054	Destabilizing	None	N	0.283	neutral	None	None	None	None	N
N/S	0.0689	likely_benign	0.0711	benign	-0.933	Destabilizing	None	N	0.244	neutral	N	0.44999823	None	None	N
N/T	0.0787	likely_benign	0.076	benign	-0.672	Destabilizing	None	N	0.229	neutral	N	0.383847809	None	None	N
N/V	0.1418	likely_benign	0.141	benign	-0.319	Destabilizing	0.009	N	0.459	neutral	None	None	None	None	N
N/W	0.5221	ambiguous	0.522	ambiguous	-0.709	Destabilizing	0.788	D	0.582	neutral	None	None	None	None	N
N/Y	0.0959	likely_benign	0.0975	benign	-0.4	Destabilizing	0.017	N	0.569	neutral	N	0.490999491	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.