TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5695	17308;17309;17310	chr2:178731792;178731791;178731790	chr2:179596519;179596518;179596517
N2AB	5378	16357;16358;16359	chr2:178731792;178731791;178731790	chr2:179596519;179596518;179596517
N2A	4451	13576;13577;13578	chr2:178731792;178731791;178731790	chr2:179596519;179596518;179596517
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-40
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.3405
• 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
Q/K	None	None	0.27	N	0.413	0.22	0.158396225186	gnomAD-4.0.0	1.59124E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85835E-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
Q/A	0.4168	ambiguous	0.4238	ambiguous	-0.947	Destabilizing	0.495	N	0.421	neutral	None	None	None	None	I
Q/C	0.7546	likely_pathogenic	0.7965	pathogenic	-0.425	Destabilizing	0.995	D	0.519	neutral	None	None	None	None	I
Q/D	0.6529	likely_pathogenic	0.6756	pathogenic	-1.305	Destabilizing	0.329	N	0.432	neutral	None	None	None	None	I
Q/E	0.1227	likely_benign	0.1246	benign	-1.08	Destabilizing	0.01	N	0.247	neutral	N	0.452441103	None	None	I
Q/F	0.8156	likely_pathogenic	0.8269	pathogenic	-0.353	Destabilizing	0.944	D	0.515	neutral	None	None	None	None	I
Q/G	0.5345	ambiguous	0.5462	ambiguous	-1.394	Destabilizing	0.329	N	0.439	neutral	None	None	None	None	I
Q/H	0.2249	likely_benign	0.249	benign	-1.0	Destabilizing	0.002	N	0.248	neutral	N	0.461100658	None	None	I
Q/I	0.5602	ambiguous	0.58	pathogenic	0.253	Stabilizing	0.944	D	0.541	neutral	None	None	None	None	I
Q/K	0.1874	likely_benign	0.2141	benign	-0.451	Destabilizing	0.27	N	0.413	neutral	N	0.48770847	None	None	I
Q/L	0.2379	likely_benign	0.2509	benign	0.253	Stabilizing	0.642	D	0.483	neutral	N	0.477030116	None	None	I
Q/M	0.5164	ambiguous	0.524	ambiguous	0.545	Stabilizing	0.981	D	0.468	neutral	None	None	None	None	I
Q/N	0.3958	ambiguous	0.3954	ambiguous	-1.256	Destabilizing	0.007	N	0.254	neutral	None	None	None	None	I
Q/P	0.7243	likely_pathogenic	0.7505	pathogenic	-0.117	Destabilizing	0.917	D	0.51	neutral	N	0.508747789	None	None	I
Q/R	0.1774	likely_benign	0.2087	benign	-0.536	Destabilizing	0.006	N	0.255	neutral	N	0.466850408	None	None	I
Q/S	0.4073	ambiguous	0.397	ambiguous	-1.473	Destabilizing	0.329	N	0.421	neutral	None	None	None	None	I
Q/T	0.3361	likely_benign	0.3494	ambiguous	-1.038	Destabilizing	0.704	D	0.474	neutral	None	None	None	None	I
Q/V	0.4076	ambiguous	0.4306	ambiguous	-0.117	Destabilizing	0.828	D	0.488	neutral	None	None	None	None	I
Q/W	0.6898	likely_pathogenic	0.7389	pathogenic	-0.259	Destabilizing	0.995	D	0.529	neutral	None	None	None	None	I
Q/Y	0.5519	ambiguous	0.5741	pathogenic	0.039	Stabilizing	0.704	D	0.551	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.