TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29659	89200;89201;89202	chr2:178554136;178554135;178554134	chr2:179418863;179418862;179418861
N2AB	28018	84277;84278;84279	chr2:178554136;178554135;178554134	chr2:179418863;179418862;179418861
N2A	27091	81496;81497;81498	chr2:178554136;178554135;178554134	chr2:179418863;179418862;179418861
N2B	20594	62005;62006;62007	chr2:178554136;178554135;178554134	chr2:179418863;179418862;179418861
Novex-1	20719	62380;62381;62382	chr2:178554136;178554135;178554134	chr2:179418863;179418862;179418861
Novex-2	20786	62581;62582;62583	chr2:178554136;178554135;178554134	chr2:179418863;179418862;179418861
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-104
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.3815
• 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
A/V	None	None	None	N	0.091	0.088	0.0716867268079	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62502E-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
A/C	0.3033	likely_benign	0.3499	ambiguous	-0.78	Destabilizing	0.356	N	0.387	neutral	None	None	None	None	I
A/D	0.1764	likely_benign	0.2004	benign	-0.5	Destabilizing	0.214	N	0.548	neutral	None	None	None	None	I
A/E	0.1707	likely_benign	0.1951	benign	-0.649	Destabilizing	0.055	N	0.487	neutral	N	0.403054353	None	None	I
A/F	0.1802	likely_benign	0.2103	benign	-0.928	Destabilizing	0.214	N	0.549	neutral	None	None	None	None	I
A/G	0.1233	likely_benign	0.1463	benign	-0.414	Destabilizing	0.055	N	0.32	neutral	N	0.425259209	None	None	I
A/H	0.2902	likely_benign	0.3396	benign	-0.492	Destabilizing	0.864	D	0.48	neutral	None	None	None	None	I
A/I	0.1098	likely_benign	0.1327	benign	-0.369	Destabilizing	0.006	N	0.456	neutral	None	None	None	None	I
A/K	0.3432	ambiguous	0.4109	ambiguous	-0.723	Destabilizing	0.072	N	0.459	neutral	None	None	None	None	I
A/L	0.0971	likely_benign	0.109	benign	-0.369	Destabilizing	None	N	0.157	neutral	None	None	None	None	I
A/M	0.1149	likely_benign	0.1314	benign	-0.405	Destabilizing	0.214	N	0.453	neutral	None	None	None	None	I
A/N	0.1319	likely_benign	0.152	benign	-0.38	Destabilizing	0.214	N	0.54	neutral	None	None	None	None	I
A/P	0.3666	ambiguous	0.4666	ambiguous	-0.328	Destabilizing	0.295	N	0.45	neutral	N	0.449770865	None	None	I
A/Q	0.2151	likely_benign	0.2559	benign	-0.653	Destabilizing	0.356	N	0.457	neutral	None	None	None	None	I
A/R	0.3124	likely_benign	0.379	ambiguous	-0.267	Destabilizing	0.214	N	0.449	neutral	None	None	None	None	I
A/S	0.0692	likely_benign	0.072	benign	-0.585	Destabilizing	0.012	N	0.382	neutral	N	0.327980592	None	None	I
A/T	0.0634	likely_benign	0.0664	benign	-0.652	Destabilizing	None	N	0.09	neutral	N	0.422853623	None	None	I
A/V	0.0699	likely_benign	0.0789	benign	-0.328	Destabilizing	None	N	0.091	neutral	N	0.441708742	None	None	I
A/W	0.586	likely_pathogenic	0.6536	pathogenic	-1.077	Destabilizing	0.864	D	0.542	neutral	None	None	None	None	I
A/Y	0.3152	likely_benign	0.3609	ambiguous	-0.731	Destabilizing	0.356	N	0.557	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.