TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4935	15028;15029;15030	chr2:178735643;178735642;178735641	chr2:179600370;179600369;179600368
N2AB	4618	14077;14078;14079	chr2:178735643;178735642;178735641	chr2:179600370;179600369;179600368
N2A	3691	11296;11297;11298	chr2:178735643;178735642;178735641	chr2:179600370;179600369;179600368
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-32
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.3477
• 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
K/E	rs759432239	0.093	0.124	N	0.391	0.28	0.282179105231	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	1.66113E-04
K/E	rs759432239	0.093	0.124	N	0.391	0.28	0.282179105231	gnomAD-4.0.0	4.77445E-06	None	None	None	None	N	None	0	0	None	0	2.77685E-05	None	1.88416E-05	0	0	0	3.02535E-05

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
K/A	0.2717	likely_benign	0.311	benign	-0.545	Destabilizing	0.072	N	0.404	neutral	None	None	None	None	N
K/C	0.5143	ambiguous	0.5404	ambiguous	-0.679	Destabilizing	0.968	D	0.576	neutral	None	None	None	None	N
K/D	0.4888	ambiguous	0.546	ambiguous	-0.127	Destabilizing	0.567	D	0.407	neutral	None	None	None	None	N
K/E	0.1535	likely_benign	0.1828	benign	-0.015	Destabilizing	0.124	N	0.391	neutral	N	0.507787521	None	None	N
K/F	0.5865	likely_pathogenic	0.6323	pathogenic	-0.234	Destabilizing	0.567	D	0.559	neutral	None	None	None	None	N
K/G	0.3451	ambiguous	0.3789	ambiguous	-0.915	Destabilizing	0.272	N	0.453	neutral	None	None	None	None	N
K/H	0.1893	likely_benign	0.2045	benign	-1.263	Destabilizing	0.909	D	0.498	neutral	None	None	None	None	N
K/I	0.2309	likely_benign	0.256	benign	0.409	Stabilizing	0.396	N	0.531	neutral	None	None	None	None	N
K/L	0.2428	likely_benign	0.2729	benign	0.409	Stabilizing	0.06	N	0.429	neutral	None	None	None	None	N
K/M	0.1861	likely_benign	0.2089	benign	0.24	Stabilizing	0.055	N	0.372	neutral	N	0.512039857	None	None	N
K/N	0.3068	likely_benign	0.3456	ambiguous	-0.519	Destabilizing	0.22	N	0.385	neutral	N	0.512949653	None	None	N
K/P	0.7742	likely_pathogenic	0.8024	pathogenic	0.121	Stabilizing	0.726	D	0.469	neutral	None	None	None	None	N
K/Q	0.1029	likely_benign	0.1118	benign	-0.584	Destabilizing	0.497	N	0.421	neutral	N	0.479442906	None	None	N
K/R	0.0639	likely_benign	0.0648	benign	-0.678	Destabilizing	0.001	N	0.133	neutral	N	0.473387815	None	None	N
K/S	0.2953	likely_benign	0.3357	benign	-1.182	Destabilizing	0.014	N	0.198	neutral	None	None	None	None	N
K/T	0.1423	likely_benign	0.1619	benign	-0.86	Destabilizing	0.124	N	0.421	neutral	N	0.401365706	None	None	N
K/V	0.2163	likely_benign	0.2449	benign	0.121	Stabilizing	0.157	N	0.429	neutral	None	None	None	None	N
K/W	0.51	ambiguous	0.5177	ambiguous	-0.107	Destabilizing	0.968	D	0.641	neutral	None	None	None	None	N
K/Y	0.4305	ambiguous	0.4612	ambiguous	0.189	Stabilizing	0.726	D	0.542	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.