TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6454	19585;19586;19587	chr2:178728566;178728565;178728564	chr2:179593293;179593292;179593291
N2AB	6137	18634;18635;18636	chr2:178728566;178728565;178728564	chr2:179593293;179593292;179593291
N2A	5210	15853;15854;15855	chr2:178728566;178728565;178728564	chr2:179593293;179593292;179593291
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-48
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.2453
• 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/L	None	None	0.012	N	0.363	0.219	0.275215494804	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	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	0.1735	likely_benign	0.1667	benign	-0.945	Destabilizing	None	N	0.177	neutral	None	None	None	None	N
Q/C	0.5641	likely_pathogenic	0.5449	ambiguous	-0.163	Destabilizing	0.356	N	0.501	neutral	None	None	None	None	N
Q/D	0.3493	ambiguous	0.3062	benign	-0.688	Destabilizing	0.007	N	0.247	neutral	None	None	None	None	N
Q/E	0.0727	likely_benign	0.0647	benign	-0.553	Destabilizing	None	N	0.113	neutral	N	0.378175418	None	None	N
Q/F	0.5472	ambiguous	0.518	ambiguous	-0.6	Destabilizing	0.356	N	0.558	neutral	None	None	None	None	N
Q/G	0.3021	likely_benign	0.2596	benign	-1.326	Destabilizing	0.016	N	0.344	neutral	None	None	None	None	N
Q/H	0.1917	likely_benign	0.1753	benign	-1.097	Destabilizing	0.295	N	0.404	neutral	N	0.493655794	None	None	N
Q/I	0.2322	likely_benign	0.2193	benign	0.049	Stabilizing	0.072	N	0.503	neutral	None	None	None	None	N
Q/K	0.0785	likely_benign	0.0687	benign	-0.354	Destabilizing	0.005	N	0.264	neutral	N	0.455692052	None	None	N
Q/L	0.104	likely_benign	0.0974	benign	0.049	Stabilizing	0.012	N	0.363	neutral	N	0.422467699	None	None	N
Q/M	0.2621	likely_benign	0.2568	benign	0.574	Stabilizing	0.628	D	0.411	neutral	None	None	None	None	N
Q/N	0.2176	likely_benign	0.201	benign	-0.959	Destabilizing	0.031	N	0.339	neutral	None	None	None	None	N
Q/P	0.1284	likely_benign	0.1208	benign	-0.252	Destabilizing	0.106	N	0.429	neutral	N	0.508507816	None	None	N
Q/R	0.0927	likely_benign	0.0864	benign	-0.341	Destabilizing	0.012	N	0.361	neutral	N	0.459484505	None	None	N
Q/S	0.2061	likely_benign	0.202	benign	-1.149	Destabilizing	0.007	N	0.241	neutral	None	None	None	None	N
Q/T	0.1562	likely_benign	0.1482	benign	-0.806	Destabilizing	None	N	0.185	neutral	None	None	None	None	N
Q/V	0.164	likely_benign	0.1601	benign	-0.252	Destabilizing	0.016	N	0.367	neutral	None	None	None	None	N
Q/W	0.4338	ambiguous	0.3899	ambiguous	-0.428	Destabilizing	0.864	D	0.509	neutral	None	None	None	None	N
Q/Y	0.3729	ambiguous	0.3396	benign	-0.204	Destabilizing	0.628	D	0.513	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.