TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28043	84352;84353;84354	chr2:178562005;178562004;178562003	chr2:179426732;179426731;179426730
N2AB	26402	79429;79430;79431	chr2:178562005;178562004;178562003	chr2:179426732;179426731;179426730
N2A	25475	76648;76649;76650	chr2:178562005;178562004;178562003	chr2:179426732;179426731;179426730
N2B	18978	57157;57158;57159	chr2:178562005;178562004;178562003	chr2:179426732;179426731;179426730
Novex-1	19103	57532;57533;57534	chr2:178562005;178562004;178562003	chr2:179426732;179426731;179426730
Novex-2	19170	57733;57734;57735	chr2:178562005;178562004;178562003	chr2:179426732;179426731;179426730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-142
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.485
• Predicted PPI site: I

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
S/Y	rs764567496	-0.46	0.295	N	0.59	0.335	0.646638679674	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.93E-06	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
S/A	0.0871	likely_benign	0.0901	benign	-0.527	Destabilizing	None	N	0.165	neutral	D	0.524285345	None	None	I
S/C	0.1077	likely_benign	0.1089	benign	-0.33	Destabilizing	0.295	N	0.521	neutral	N	0.511954247	None	None	I
S/D	0.2565	likely_benign	0.2635	benign	0.083	Stabilizing	0.072	N	0.383	neutral	None	None	None	None	I
S/E	0.2937	likely_benign	0.293	benign	-0.012	Destabilizing	0.072	N	0.359	neutral	None	None	None	None	I
S/F	0.1714	likely_benign	0.1878	benign	-1.122	Destabilizing	0.295	N	0.585	neutral	D	0.533656977	None	None	I
S/G	0.1114	likely_benign	0.1175	benign	-0.635	Destabilizing	0.016	N	0.367	neutral	None	None	None	None	I
S/H	0.2388	likely_benign	0.24	benign	-1.171	Destabilizing	0.628	D	0.521	neutral	None	None	None	None	I
S/I	0.1339	likely_benign	0.1341	benign	-0.368	Destabilizing	0.038	N	0.567	neutral	None	None	None	None	I
S/K	0.4165	ambiguous	0.422	ambiguous	-0.51	Destabilizing	0.072	N	0.371	neutral	None	None	None	None	I
S/L	0.0998	likely_benign	0.1047	benign	-0.368	Destabilizing	0.016	N	0.553	neutral	None	None	None	None	I
S/M	0.1544	likely_benign	0.1545	benign	0.001	Stabilizing	0.356	N	0.537	neutral	None	None	None	None	I
S/N	0.092	likely_benign	0.0895	benign	-0.233	Destabilizing	0.072	N	0.443	neutral	None	None	None	None	I
S/P	0.5739	likely_pathogenic	0.6146	pathogenic	-0.394	Destabilizing	None	N	0.276	neutral	N	0.500344452	None	None	I
S/Q	0.3078	likely_benign	0.3067	benign	-0.528	Destabilizing	0.356	N	0.48	neutral	None	None	None	None	I
S/R	0.38	ambiguous	0.3923	ambiguous	-0.292	Destabilizing	0.214	N	0.564	neutral	None	None	None	None	I
S/T	0.0655	likely_benign	0.0635	benign	-0.368	Destabilizing	None	N	0.165	neutral	N	0.456580273	None	None	I
S/V	0.1337	likely_benign	0.1319	benign	-0.394	Destabilizing	None	N	0.365	neutral	None	None	None	None	I
S/W	0.3289	likely_benign	0.3674	ambiguous	-1.082	Destabilizing	0.864	D	0.587	neutral	None	None	None	None	I
S/Y	0.1623	likely_benign	0.1757	benign	-0.821	Destabilizing	0.295	N	0.59	neutral	N	0.500344452	None	None	I

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.