TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9128	27607;27608;27609	chr2:178712540;178712539;178712538	chr2:179577267;179577266;179577265
N2AB	8811	26656;26657;26658	chr2:178712540;178712539;178712538	chr2:179577267;179577266;179577265
N2A	7884	23875;23876;23877	chr2:178712540;178712539;178712538	chr2:179577267;179577266;179577265
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-77
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4268
• Predicted PPI site: I

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
P/L	None	None	0.521	N	0.382	0.122	0.323886383625	gnomAD-4.0.0	1.36872E-06	None	None	None	None	I	None	2.98829E-05	0	None	0	0	None	0	0	8.9957E-07	0	0
P/S	rs1283675898	-0.945	0.028	N	0.218	0.051	0.107399877778	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/S	rs1283675898	-0.945	0.028	N	0.218	0.051	0.107399877778	gnomAD-4.0.0	3.18424E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86615E-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
P/A	0.0796	likely_benign	0.0723	benign	-1.121	Destabilizing	0.007	N	0.221	neutral	N	0.507733372	None	None	I
P/C	0.4796	ambiguous	0.4008	ambiguous	-0.898	Destabilizing	0.987	D	0.392	neutral	None	None	None	None	I
P/D	0.3977	ambiguous	0.363	ambiguous	-0.615	Destabilizing	0.59	D	0.283	neutral	None	None	None	None	I
P/E	0.3052	likely_benign	0.2925	benign	-0.635	Destabilizing	0.59	D	0.312	neutral	None	None	None	None	I
P/F	0.3857	ambiguous	0.345	ambiguous	-0.846	Destabilizing	0.953	D	0.384	neutral	None	None	None	None	I
P/G	0.259	likely_benign	0.239	benign	-1.404	Destabilizing	0.59	D	0.342	neutral	None	None	None	None	I
P/H	0.1714	likely_benign	0.1395	benign	-0.812	Destabilizing	0.939	D	0.359	neutral	N	0.463529701	None	None	I
P/I	0.2673	likely_benign	0.2493	benign	-0.466	Destabilizing	0.91	D	0.404	neutral	None	None	None	None	I
P/K	0.3021	likely_benign	0.2929	benign	-0.941	Destabilizing	0.037	N	0.208	neutral	None	None	None	None	I
P/L	0.1157	likely_benign	0.1057	benign	-0.466	Destabilizing	0.521	D	0.382	neutral	N	0.502962271	None	None	I
P/M	0.271	likely_benign	0.2497	benign	-0.443	Destabilizing	0.987	D	0.359	neutral	None	None	None	None	I
P/N	0.2262	likely_benign	0.2004	benign	-0.734	Destabilizing	0.02	N	0.251	neutral	None	None	None	None	I
P/Q	0.1566	likely_benign	0.1444	benign	-0.886	Destabilizing	0.082	N	0.241	neutral	None	None	None	None	I
P/R	0.1904	likely_benign	0.1826	benign	-0.423	Destabilizing	0.521	D	0.346	neutral	N	0.491398483	None	None	I
P/S	0.1034	likely_benign	0.0926	benign	-1.284	Destabilizing	0.028	N	0.218	neutral	N	0.414628423	None	None	I
P/T	0.0999	likely_benign	0.0922	benign	-1.184	Destabilizing	0.521	D	0.298	neutral	N	0.445239332	None	None	I
P/V	0.1889	likely_benign	0.176	benign	-0.648	Destabilizing	0.59	D	0.332	neutral	None	None	None	None	I
P/W	0.574	likely_pathogenic	0.524	ambiguous	-0.976	Destabilizing	0.996	D	0.554	neutral	None	None	None	None	I
P/Y	0.324	likely_benign	0.2869	benign	-0.693	Destabilizing	0.984	D	0.389	neutral	None	None	None	None	I

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.