TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8314	25165;25166;25167	chr2:178718066;178718065;178718064	chr2:179582793;179582792;179582791
N2AB	7997	24214;24215;24216	chr2:178718066;178718065;178718064	chr2:179582793;179582792;179582791
N2A	7070	21433;21434;21435	chr2:178718066;178718065;178718064	chr2:179582793;179582792;179582791
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-68
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.2327
• 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
F/L	rs570367600	-1.189	0.014	N	0.321	0.263	0.251116650651	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	9.8E-05	None	0	0	0
F/L	rs570367600	-1.189	0.014	N	0.321	0.263	0.251116650651	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
F/L	rs570367600	-1.189	0.014	N	0.321	0.263	0.251116650651	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
F/L	rs570367600	-1.189	0.014	N	0.321	0.263	0.251116650651	gnomAD-4.0.0	1.11405E-05	None	None	None	None	N	None	0	0	None	0	2.773E-05	None	0	0	0	8.59747E-05	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
F/A	0.9538	likely_pathogenic	0.9738	pathogenic	-2.19	Highly Destabilizing	0.935	D	0.655	neutral	None	None	None	None	N
F/C	0.8497	likely_pathogenic	0.9046	pathogenic	-1.072	Destabilizing	0.999	D	0.678	prob.neutral	N	0.495011627	None	None	N
F/D	0.9809	likely_pathogenic	0.9888	pathogenic	-1.022	Destabilizing	0.981	D	0.709	prob.delet.	None	None	None	None	N
F/E	0.9711	likely_pathogenic	0.9827	pathogenic	-0.935	Destabilizing	0.684	D	0.697	prob.neutral	None	None	None	None	N
F/G	0.9725	likely_pathogenic	0.9851	pathogenic	-2.531	Highly Destabilizing	0.99	D	0.699	prob.neutral	None	None	None	None	N
F/H	0.876	likely_pathogenic	0.9213	pathogenic	-0.833	Destabilizing	0.938	D	0.649	neutral	None	None	None	None	N
F/I	0.6204	likely_pathogenic	0.7089	pathogenic	-1.166	Destabilizing	0.693	D	0.585	neutral	N	0.50769974	None	None	N
F/K	0.97	likely_pathogenic	0.9829	pathogenic	-1.28	Destabilizing	0.913	D	0.699	prob.neutral	None	None	None	None	N
F/L	0.9472	likely_pathogenic	0.9669	pathogenic	-1.166	Destabilizing	0.014	N	0.321	neutral	N	0.495674592	None	None	N
F/M	0.7824	likely_pathogenic	0.8421	pathogenic	-0.823	Destabilizing	0.662	D	0.636	neutral	None	None	None	None	N
F/N	0.9338	likely_pathogenic	0.9579	pathogenic	-1.336	Destabilizing	0.99	D	0.709	prob.delet.	None	None	None	None	N
F/P	0.9984	likely_pathogenic	0.9991	pathogenic	-1.502	Destabilizing	0.997	D	0.702	prob.neutral	None	None	None	None	N
F/Q	0.9396	likely_pathogenic	0.9657	pathogenic	-1.407	Destabilizing	0.281	N	0.543	neutral	None	None	None	None	N
F/R	0.9424	likely_pathogenic	0.9659	pathogenic	-0.622	Destabilizing	0.954	D	0.71	prob.delet.	None	None	None	None	N
F/S	0.9209	likely_pathogenic	0.9531	pathogenic	-2.103	Highly Destabilizing	0.916	D	0.693	prob.neutral	N	0.484649522	None	None	N
F/T	0.9264	likely_pathogenic	0.9544	pathogenic	-1.923	Destabilizing	0.99	D	0.696	prob.neutral	None	None	None	None	N
F/V	0.6604	likely_pathogenic	0.7484	pathogenic	-1.502	Destabilizing	0.621	D	0.583	neutral	N	0.488996549	None	None	N
F/W	0.6341	likely_pathogenic	0.7062	pathogenic	-0.356	Destabilizing	0.998	D	0.627	neutral	None	None	None	None	N
F/Y	0.2899	likely_benign	0.3397	benign	-0.575	Destabilizing	0.026	N	0.356	neutral	N	0.45690556	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.