TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4002	12229;12230;12231	chr2:178741229;178741228;178741227	chr2:179605956;179605955;179605954
N2AB	3685	11278;11279;11280	chr2:178741229;178741228;178741227	chr2:179605956;179605955;179605954
N2A	None	None	chr2:None	chr2:None
N2B	3639	11140;11141;11142	chr2:178741229;178741228;178741227	chr2:179605956;179605955;179605954
Novex-1	3764	11515;11516;11517	chr2:178741229;178741228;178741227	chr2:179605956;179605955;179605954
Novex-2	3831	11716;11717;11718	chr2:178741229;178741228;178741227	chr2:179605956;179605955;179605954
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-28
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.4374
• 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/E	None	None	0.425	N	0.269	0.176	None	gnomAD-4.0.0	1.59216E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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
Q/A	0.3459	ambiguous	0.3013	benign	-0.435	Destabilizing	0.329	N	0.333	neutral	None	None	None	None	I
Q/C	0.6494	likely_pathogenic	0.5814	pathogenic	0.194	Stabilizing	0.995	D	0.333	neutral	None	None	None	None	I
Q/D	0.5619	ambiguous	0.4946	ambiguous	-0.592	Destabilizing	0.329	N	0.181	neutral	None	None	None	None	I
Q/E	0.1116	likely_benign	0.1046	benign	-0.549	Destabilizing	0.425	N	0.269	neutral	N	0.508139942	None	None	I
Q/F	0.7471	likely_pathogenic	0.6719	pathogenic	-0.306	Destabilizing	0.893	D	0.356	neutral	None	None	None	None	I
Q/G	0.3093	likely_benign	0.2804	benign	-0.746	Destabilizing	0.329	N	0.338	neutral	None	None	None	None	I
Q/H	0.3025	likely_benign	0.2578	benign	-0.769	Destabilizing	0.927	D	0.278	neutral	D	0.553336482	None	None	I
Q/I	0.4971	ambiguous	0.4298	ambiguous	0.334	Stabilizing	0.543	D	0.375	neutral	None	None	None	None	I
Q/K	0.0849	likely_benign	0.0853	benign	-0.316	Destabilizing	0.01	N	0.111	neutral	N	0.500549486	None	None	I
Q/L	0.1683	likely_benign	0.1423	benign	0.334	Stabilizing	0.27	N	0.336	neutral	N	0.510704917	None	None	I
Q/M	0.4726	ambiguous	0.4088	ambiguous	0.853	Stabilizing	0.944	D	0.278	neutral	None	None	None	None	I
Q/N	0.4118	ambiguous	0.37	ambiguous	-0.728	Destabilizing	0.007	N	0.113	neutral	None	None	None	None	I
Q/P	0.4476	ambiguous	0.4044	ambiguous	0.109	Stabilizing	0.784	D	0.347	neutral	D	0.663077372	None	None	I
Q/R	0.1046	likely_benign	0.0975	benign	-0.209	Destabilizing	0.27	N	0.201	neutral	N	0.511272088	None	None	I
Q/S	0.3799	ambiguous	0.3363	benign	-0.746	Destabilizing	0.329	N	0.257	neutral	None	None	None	None	I
Q/T	0.3362	likely_benign	0.2942	benign	-0.528	Destabilizing	0.495	N	0.296	neutral	None	None	None	None	I
Q/V	0.3609	ambiguous	0.2991	benign	0.109	Stabilizing	0.007	N	0.184	neutral	None	None	None	None	I
Q/W	0.6294	likely_pathogenic	0.5632	ambiguous	-0.241	Destabilizing	0.995	D	0.349	neutral	None	None	None	None	I
Q/Y	0.5987	likely_pathogenic	0.5214	ambiguous	-0.013	Destabilizing	0.944	D	0.331	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.