TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3095	9508;9509;9510	chr2:178768036;178768035;178768034	chr2:179632763;179632762;179632761
N2AB	3095	9508;9509;9510	chr2:178768036;178768035;178768034	chr2:179632763;179632762;179632761
N2A	3095	9508;9509;9510	chr2:178768036;178768035;178768034	chr2:179632763;179632762;179632761
N2B	3049	9370;9371;9372	chr2:178768036;178768035;178768034	chr2:179632763;179632762;179632761
Novex-1	3049	9370;9371;9372	chr2:178768036;178768035;178768034	chr2:179632763;179632762;179632761
Novex-2	3049	9370;9371;9372	chr2:178768036;178768035;178768034	chr2:179632763;179632762;179632761
Novex-3	3095	9508;9509;9510	chr2:178768036;178768035;178768034	chr2:179632763;179632762;179632761

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-21
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.5165
• 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/R	None	None	0.722	N	0.483	0.395	0.301789629655	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3736	ambiguous	0.3308	benign	-0.151	Destabilizing	0.775	D	0.475	neutral	None	None	None	None	N
Q/C	0.7983	likely_pathogenic	0.767	pathogenic	0.263	Stabilizing	0.996	D	0.579	neutral	None	None	None	None	N
Q/D	0.654	likely_pathogenic	0.5928	pathogenic	-0.088	Destabilizing	0.775	D	0.446	neutral	None	None	None	None	N
Q/E	0.1121	likely_benign	0.1044	benign	-0.126	Destabilizing	0.517	D	0.454	neutral	N	0.497755123	None	None	N
Q/F	0.8431	likely_pathogenic	0.8117	pathogenic	-0.38	Destabilizing	0.923	D	0.557	neutral	None	None	None	None	N
Q/G	0.5367	ambiguous	0.4684	ambiguous	-0.33	Destabilizing	0.775	D	0.454	neutral	None	None	None	None	N
Q/H	0.3543	ambiguous	0.3198	benign	-0.261	Destabilizing	0.018	N	0.231	neutral	D	0.546256747	None	None	N
Q/I	0.4219	ambiguous	0.3939	ambiguous	0.23	Stabilizing	0.961	D	0.549	neutral	None	None	None	None	N
Q/K	0.1136	likely_benign	0.1002	benign	0.032	Stabilizing	0.722	D	0.497	neutral	N	0.506996888	None	None	N
Q/L	0.2475	likely_benign	0.2216	benign	0.23	Stabilizing	0.722	D	0.429	neutral	N	0.512078711	None	None	N
Q/M	0.4046	ambiguous	0.3887	ambiguous	0.465	Stabilizing	0.987	D	0.42	neutral	None	None	None	None	N
Q/N	0.4484	ambiguous	0.4118	ambiguous	-0.157	Destabilizing	0.633	D	0.429	neutral	None	None	None	None	N
Q/P	0.9446	likely_pathogenic	0.9022	pathogenic	0.131	Stabilizing	0.983	D	0.439	neutral	D	0.695423188	None	None	N
Q/R	0.1423	likely_benign	0.1242	benign	0.203	Stabilizing	0.722	D	0.483	neutral	N	0.515685191	None	None	N
Q/S	0.4464	ambiguous	0.4031	ambiguous	-0.156	Destabilizing	0.775	D	0.449	neutral	None	None	None	None	N
Q/T	0.2954	likely_benign	0.2668	benign	-0.053	Destabilizing	0.875	D	0.419	neutral	None	None	None	None	N
Q/V	0.3011	likely_benign	0.2792	benign	0.131	Stabilizing	0.961	D	0.412	neutral	None	None	None	None	N
Q/W	0.8303	likely_pathogenic	0.7799	pathogenic	-0.393	Destabilizing	0.996	D	0.545	neutral	None	None	None	None	N
Q/Y	0.703	likely_pathogenic	0.6627	pathogenic	-0.135	Destabilizing	0.858	D	0.439	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.