TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8756	26491;26492;26493	chr2:178714508;178714507;178714506	chr2:179579235;179579234;179579233
N2AB	8439	25540;25541;25542	chr2:178714508;178714507;178714506	chr2:179579235;179579234;179579233
N2A	7512	22759;22760;22761	chr2:178714508;178714507;178714506	chr2:179579235;179579234;179579233
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-73
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4193
• 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
Q/H	rs776025006	-0.967	0.993	N	0.529	0.304	0.346315397577	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/H	rs776025006	-0.967	0.993	N	0.529	0.304	0.346315397577	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43377E-05	0
Q/R	rs761090454	-0.06	0.901	N	0.506	0.199	0.225215365344	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	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	0.2358	likely_benign	0.2873	benign	-0.686	Destabilizing	0.904	D	0.472	neutral	None	None	None	None	N
Q/C	0.5507	ambiguous	0.6816	pathogenic	-0.089	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
Q/D	0.3717	ambiguous	0.4745	ambiguous	-0.282	Destabilizing	0.977	D	0.485	neutral	None	None	None	None	N
Q/E	0.0757	likely_benign	0.0838	benign	-0.193	Destabilizing	0.948	D	0.469	neutral	N	0.443205544	None	None	N
Q/F	0.5874	likely_pathogenic	0.696	pathogenic	-0.373	Destabilizing	0.978	D	0.623	neutral	None	None	None	None	N
Q/G	0.269	likely_benign	0.3495	ambiguous	-1.03	Destabilizing	0.979	D	0.556	neutral	None	None	None	None	N
Q/H	0.1926	likely_benign	0.2456	benign	-0.783	Destabilizing	0.993	D	0.529	neutral	N	0.491506135	None	None	N
Q/I	0.3203	likely_benign	0.3848	ambiguous	0.185	Stabilizing	0.819	D	0.552	neutral	None	None	None	None	N
Q/K	0.0917	likely_benign	0.107	benign	-0.232	Destabilizing	0.933	D	0.481	neutral	D	0.522359761	None	None	N
Q/L	0.1351	likely_benign	0.1722	benign	0.185	Stabilizing	0.021	N	0.393	neutral	N	0.516377938	None	None	N
Q/M	0.3314	likely_benign	0.3905	ambiguous	0.569	Stabilizing	0.45	N	0.343	neutral	None	None	None	None	N
Q/N	0.3057	likely_benign	0.3698	ambiguous	-0.765	Destabilizing	0.993	D	0.525	neutral	None	None	None	None	N
Q/P	0.351	ambiguous	0.5305	ambiguous	-0.074	Destabilizing	0.991	D	0.573	neutral	N	0.488948467	None	None	N
Q/R	0.0928	likely_benign	0.1123	benign	-0.15	Destabilizing	0.901	D	0.506	neutral	N	0.518012734	None	None	N
Q/S	0.2582	likely_benign	0.3015	benign	-0.915	Destabilizing	0.979	D	0.453	neutral	None	None	None	None	N
Q/T	0.1796	likely_benign	0.2156	benign	-0.626	Destabilizing	0.641	D	0.483	neutral	None	None	None	None	N
Q/V	0.2209	likely_benign	0.2615	benign	-0.074	Destabilizing	0.577	D	0.525	neutral	None	None	None	None	N
Q/W	0.4039	ambiguous	0.5641	pathogenic	-0.188	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
Q/Y	0.3968	ambiguous	0.5104	ambiguous	0.014	Stabilizing	0.996	D	0.581	neutral	None	None	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.