TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3098	9517;9518;9519	chr2:178768027;178768026;178768025	chr2:179632754;179632753;179632752
N2AB	3098	9517;9518;9519	chr2:178768027;178768026;178768025	chr2:179632754;179632753;179632752
N2A	3098	9517;9518;9519	chr2:178768027;178768026;178768025	chr2:179632754;179632753;179632752
N2B	3052	9379;9380;9381	chr2:178768027;178768026;178768025	chr2:179632754;179632753;179632752
Novex-1	3052	9379;9380;9381	chr2:178768027;178768026;178768025	chr2:179632754;179632753;179632752
Novex-2	3052	9379;9380;9381	chr2:178768027;178768026;178768025	chr2:179632754;179632753;179632752
Novex-3	3098	9517;9518;9519	chr2:178768027;178768026;178768025	chr2:179632754;179632753;179632752

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-21
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.7922
• 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/E	None	None	0.001	N	0.177	0.167	0.168933306366	gnomAD-4.0.0	3.42037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49647E-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	0.2077	likely_benign	0.158	benign	-0.025	Destabilizing	0.035	N	0.347	neutral	None	None	None	None	N
Q/C	0.7182	likely_pathogenic	0.635	pathogenic	-0.161	Destabilizing	0.935	D	0.322	neutral	None	None	None	None	N
Q/D	0.3441	ambiguous	0.264	benign	-0.105	Destabilizing	0.035	N	0.316	neutral	None	None	None	None	N
Q/E	0.094	likely_benign	0.0871	benign	-0.147	Destabilizing	0.001	N	0.177	neutral	N	0.445463093	None	None	N
Q/F	0.6819	likely_pathogenic	0.5985	pathogenic	-0.428	Destabilizing	0.38	N	0.335	neutral	None	None	None	None	N
Q/G	0.3275	likely_benign	0.2525	benign	-0.141	Destabilizing	0.149	N	0.383	neutral	None	None	None	None	N
Q/H	0.2069	likely_benign	0.1693	benign	0.087	Stabilizing	None	N	0.193	neutral	N	0.510439237	None	None	N
Q/I	0.3374	likely_benign	0.3093	benign	0.183	Stabilizing	0.555	D	0.357	neutral	None	None	None	None	N
Q/K	0.1237	likely_benign	0.1025	benign	-0.001	Destabilizing	0.052	N	0.342	neutral	N	0.482056386	None	None	N
Q/L	0.1334	likely_benign	0.1219	benign	0.183	Stabilizing	0.117	N	0.385	neutral	N	0.483925839	None	None	N
Q/M	0.3239	likely_benign	0.2906	benign	0.027	Stabilizing	0.791	D	0.318	neutral	None	None	None	None	N
Q/N	0.2385	likely_benign	0.1866	benign	-0.332	Destabilizing	0.081	N	0.295	neutral	None	None	None	None	N
Q/P	0.0878	likely_benign	0.0685	benign	0.138	Stabilizing	None	N	0.167	neutral	N	0.488625352	None	None	N
Q/R	0.1527	likely_benign	0.1254	benign	0.191	Stabilizing	0.117	N	0.321	neutral	N	0.494779425	None	None	N
Q/S	0.229	likely_benign	0.1662	benign	-0.277	Destabilizing	0.067	N	0.31	neutral	None	None	None	None	N
Q/T	0.1958	likely_benign	0.1603	benign	-0.192	Destabilizing	0.149	N	0.364	neutral	None	None	None	None	N
Q/V	0.225	likely_benign	0.2034	benign	0.138	Stabilizing	0.149	N	0.381	neutral	None	None	None	None	N
Q/W	0.6203	likely_pathogenic	0.4935	ambiguous	-0.527	Destabilizing	0.935	D	0.336	neutral	None	None	None	None	N
Q/Y	0.4882	ambiguous	0.408	ambiguous	-0.217	Destabilizing	0.235	N	0.34	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.