TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4856	14791;14792;14793	chr2:178735880;178735879;178735878	chr2:179600607;179600606;179600605
N2AB	4539	13840;13841;13842	chr2:178735880;178735879;178735878	chr2:179600607;179600606;179600605
N2A	3612	11059;11060;11061	chr2:178735880;178735879;178735878	chr2:179600607;179600606;179600605
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-31
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.4297
• 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
N/K	None	None	0.27	N	0.229	0.103	0.0551355673512	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85796E-06	0	0
N/S	None	None	0.065	N	0.134	0.122	0.124217242631	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	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
N/A	0.2299	likely_benign	0.1664	benign	-0.35	Destabilizing	0.329	N	0.345	neutral	None	None	None	None	N
N/C	0.3121	likely_benign	0.2366	benign	0.423	Stabilizing	0.017	N	0.271	neutral	None	None	None	None	N
N/D	0.1197	likely_benign	0.0919	benign	0.054	Stabilizing	0.642	D	0.223	neutral	N	0.346238992	None	None	N
N/E	0.3528	ambiguous	0.2564	benign	0.003	Stabilizing	0.329	N	0.218	neutral	None	None	None	None	N
N/F	0.5109	ambiguous	0.3776	ambiguous	-0.794	Destabilizing	0.893	D	0.417	neutral	None	None	None	None	N
N/G	0.2361	likely_benign	0.1862	benign	-0.496	Destabilizing	0.495	N	0.225	neutral	None	None	None	None	N
N/H	0.1004	likely_benign	0.0857	benign	-0.586	Destabilizing	0.927	D	0.329	neutral	N	0.370354707	None	None	N
N/I	0.3218	likely_benign	0.2356	benign	-0.056	Destabilizing	0.473	N	0.431	neutral	N	0.437917218	None	None	N
N/K	0.2545	likely_benign	0.1903	benign	0.2	Stabilizing	0.27	N	0.229	neutral	N	0.329601975	None	None	N
N/L	0.2704	likely_benign	0.2	benign	-0.056	Destabilizing	0.007	N	0.253	neutral	None	None	None	None	N
N/M	0.4127	ambiguous	0.3167	benign	0.424	Stabilizing	0.893	D	0.396	neutral	None	None	None	None	N
N/P	0.6595	likely_pathogenic	0.5789	pathogenic	-0.129	Destabilizing	0.944	D	0.434	neutral	None	None	None	None	N
N/Q	0.3079	likely_benign	0.2334	benign	-0.269	Destabilizing	0.085	N	0.235	neutral	None	None	None	None	N
N/R	0.2571	likely_benign	0.2003	benign	0.285	Stabilizing	0.007	N	0.213	neutral	None	None	None	None	N
N/S	0.085	likely_benign	0.0767	benign	0.004	Stabilizing	0.065	N	0.134	neutral	N	0.337557114	None	None	N
N/T	0.1867	likely_benign	0.1463	benign	0.085	Stabilizing	0.27	N	0.219	neutral	N	0.403085728	None	None	N
N/V	0.3039	likely_benign	0.2216	benign	-0.129	Destabilizing	0.543	D	0.431	neutral	None	None	None	None	N
N/W	0.7867	likely_pathogenic	0.683	pathogenic	-0.775	Destabilizing	0.995	D	0.417	neutral	None	None	None	None	N
N/Y	0.1651	likely_benign	0.1281	benign	-0.502	Destabilizing	0.927	D	0.395	neutral	N	0.422279857	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.