TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17931	54016;54017;54018	chr2:178605504;178605503;178605502	chr2:179470231;179470230;179470229
N2AB	16290	49093;49094;49095	chr2:178605504;178605503;178605502	chr2:179470231;179470230;179470229
N2A	15363	46312;46313;46314	chr2:178605504;178605503;178605502	chr2:179470231;179470230;179470229
N2B	8866	26821;26822;26823	chr2:178605504;178605503;178605502	chr2:179470231;179470230;179470229
Novex-1	8991	27196;27197;27198	chr2:178605504;178605503;178605502	chr2:179470231;179470230;179470229
Novex-2	9058	27397;27398;27399	chr2:178605504;178605503;178605502	chr2:179470231;179470230;179470229
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-18
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1632
• 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	rs759208053	-1.615	0.425	N	0.335	0.169	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.6559E-04	0	None	0	0	None	0	None	0	0	0
Q/E	rs759208053	-1.615	0.425	N	0.335	0.169	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	1.44949E-04	0	0	0	0	None	0	0	0	0	0
Q/E	rs759208053	-1.615	0.425	N	0.335	0.169	None	gnomAD-4.0.0	6.20302E-06	None	None	None	None	N	None	1.33711E-04	0	None	0	0	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	0.286	likely_benign	0.2506	benign	-0.812	Destabilizing	0.495	N	0.362	neutral	None	None	None	None	N
Q/C	0.5357	ambiguous	0.4444	ambiguous	-0.187	Destabilizing	0.995	D	0.475	neutral	None	None	None	None	N
Q/D	0.5172	ambiguous	0.4377	ambiguous	-1.304	Destabilizing	0.704	D	0.297	neutral	None	None	None	None	N
Q/E	0.1101	likely_benign	0.1067	benign	-1.091	Destabilizing	0.425	N	0.335	neutral	N	0.432265327	None	None	N
Q/F	0.6348	likely_pathogenic	0.5617	ambiguous	-0.185	Destabilizing	0.893	D	0.526	neutral	None	None	None	None	N
Q/G	0.4041	ambiguous	0.3393	benign	-1.263	Destabilizing	0.704	D	0.39	neutral	None	None	None	None	N
Q/H	0.2067	likely_benign	0.1433	benign	-0.97	Destabilizing	0.002	N	0.069	neutral	N	0.427648941	None	None	N
Q/I	0.5247	ambiguous	0.5178	ambiguous	0.402	Stabilizing	0.944	D	0.529	neutral	None	None	None	None	N
Q/K	0.1733	likely_benign	0.1516	benign	-0.64	Destabilizing	0.642	D	0.297	neutral	N	0.435324274	None	None	N
Q/L	0.1953	likely_benign	0.1809	benign	0.402	Stabilizing	0.642	D	0.375	neutral	N	0.449293649	None	None	N
Q/M	0.3695	ambiguous	0.358	ambiguous	0.738	Stabilizing	0.981	D	0.39	neutral	None	None	None	None	N
Q/N	0.3273	likely_benign	0.2572	benign	-1.385	Destabilizing	0.704	D	0.294	neutral	None	None	None	None	N
Q/P	0.8863	likely_pathogenic	0.8876	pathogenic	0.027	Stabilizing	0.975	D	0.456	neutral	N	0.471875764	None	None	N
Q/R	0.169	likely_benign	0.1481	benign	-0.743	Destabilizing	0.642	D	0.324	neutral	N	0.435265559	None	None	N
Q/S	0.3025	likely_benign	0.2389	benign	-1.529	Destabilizing	0.704	D	0.266	neutral	None	None	None	None	N
Q/T	0.2942	likely_benign	0.2613	benign	-1.117	Destabilizing	0.828	D	0.394	neutral	None	None	None	None	N
Q/V	0.3224	likely_benign	0.3199	benign	0.027	Stabilizing	0.828	D	0.481	neutral	None	None	None	None	N
Q/W	0.6335	likely_pathogenic	0.5844	pathogenic	-0.198	Destabilizing	0.003	N	0.167	neutral	None	None	None	None	N
Q/Y	0.4461	ambiguous	0.361	ambiguous	0.102	Stabilizing	0.704	D	0.39	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.