TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23768	71527;71528;71529	chr2:178574830;178574829;178574828	chr2:179439557;179439556;179439555
N2AB	22127	66604;66605;66606	chr2:178574830;178574829;178574828	chr2:179439557;179439556;179439555
N2A	21200	63823;63824;63825	chr2:178574830;178574829;178574828	chr2:179439557;179439556;179439555
N2B	14703	44332;44333;44334	chr2:178574830;178574829;178574828	chr2:179439557;179439556;179439555
Novex-1	14828	44707;44708;44709	chr2:178574830;178574829;178574828	chr2:179439557;179439556;179439555
Novex-2	14895	44908;44909;44910	chr2:178574830;178574829;178574828	chr2:179439557;179439556;179439555
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: Fn3-60
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.2247
• 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/P	None	None	0.784	N	0.483	0.302	0.317378411342	gnomAD-4.0.0	6.16112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09779E-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	0.2225	likely_benign	0.221	benign	-0.813	Destabilizing	0.495	N	0.387	neutral	None	None	None	None	N
Q/C	0.7258	likely_pathogenic	0.7231	pathogenic	-0.075	Destabilizing	0.995	D	0.573	neutral	None	None	None	None	N
Q/D	0.452	ambiguous	0.4801	ambiguous	-0.681	Destabilizing	0.176	N	0.259	neutral	None	None	None	None	N
Q/E	0.0878	likely_benign	0.0939	benign	-0.562	Destabilizing	0.001	N	0.083	neutral	N	0.32885017	None	None	N
Q/F	0.8658	likely_pathogenic	0.8685	pathogenic	-0.449	Destabilizing	0.981	D	0.573	neutral	None	None	None	None	N
Q/G	0.3243	likely_benign	0.3255	benign	-1.194	Destabilizing	0.495	N	0.472	neutral	None	None	None	None	N
Q/H	0.3306	likely_benign	0.3262	benign	-0.98	Destabilizing	0.927	D	0.441	neutral	N	0.494855368	None	None	N
Q/I	0.572	likely_pathogenic	0.5604	ambiguous	0.173	Stabilizing	0.944	D	0.585	neutral	None	None	None	None	N
Q/K	0.0993	likely_benign	0.0934	benign	-0.447	Destabilizing	0.002	N	0.086	neutral	N	0.409716541	None	None	N
Q/L	0.1969	likely_benign	0.2004	benign	0.173	Stabilizing	0.425	N	0.521	neutral	N	0.453374104	None	None	N
Q/M	0.4331	ambiguous	0.4333	ambiguous	0.666	Stabilizing	0.981	D	0.468	neutral	None	None	None	None	N
Q/N	0.3158	likely_benign	0.3324	benign	-1.034	Destabilizing	0.495	N	0.371	neutral	None	None	None	None	N
Q/P	0.1408	likely_benign	0.1363	benign	-0.124	Destabilizing	0.784	D	0.483	neutral	N	0.433342762	None	None	N
Q/R	0.1339	likely_benign	0.129	benign	-0.391	Destabilizing	0.27	N	0.395	neutral	N	0.420608325	None	None	N
Q/S	0.2939	likely_benign	0.2998	benign	-1.156	Destabilizing	0.495	N	0.337	neutral	None	None	None	None	N
Q/T	0.2828	likely_benign	0.2774	benign	-0.833	Destabilizing	0.495	N	0.487	neutral	None	None	None	None	N
Q/V	0.3416	ambiguous	0.3387	benign	-0.124	Destabilizing	0.828	D	0.52	neutral	None	None	None	None	N
Q/W	0.8255	likely_pathogenic	0.8335	pathogenic	-0.313	Destabilizing	0.995	D	0.556	neutral	None	None	None	None	N
Q/Y	0.6947	likely_pathogenic	0.7022	pathogenic	-0.102	Destabilizing	0.981	D	0.553	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.