TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7620	23083;23084;23085	chr2:178721161;178721160;178721159	chr2:179585888;179585887;179585886
N2AB	7303	22132;22133;22134	chr2:178721161;178721160;178721159	chr2:179585888;179585887;179585886
N2A	6376	19351;19352;19353	chr2:178721161;178721160;178721159	chr2:179585888;179585887;179585886
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-61
• Domain position: 13
• Structural Position: 17
• Q(SASA): 0.2815
• 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
A/S	rs749462228	-1.093	0.193	N	0.4	0.248	0.346315397577	gnomAD-4.0.0	6.86986E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02939E-07	0	0
A/V	rs2078299503	None	0.001	N	0.103	0.14	0.301789629655	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/V	rs2078299503	None	0.001	N	0.103	0.14	0.301789629655	gnomAD-4.0.0	2.02998E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40988E-06	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
A/C	0.4429	ambiguous	0.4566	ambiguous	-0.896	Destabilizing	0.944	D	0.497	neutral	None	None	None	None	N
A/D	0.6134	likely_pathogenic	0.6171	pathogenic	-1.538	Destabilizing	0.002	N	0.321	neutral	None	None	None	None	N
A/E	0.4401	ambiguous	0.4847	ambiguous	-1.544	Destabilizing	0.193	N	0.45	neutral	N	0.494562658	None	None	N
A/F	0.3184	likely_benign	0.3581	ambiguous	-0.99	Destabilizing	0.69	D	0.546	neutral	None	None	None	None	N
A/G	0.1506	likely_benign	0.1448	benign	-1.285	Destabilizing	0.001	N	0.135	neutral	N	0.501931348	None	None	N
A/H	0.6586	likely_pathogenic	0.67	pathogenic	-1.522	Destabilizing	0.981	D	0.509	neutral	None	None	None	None	N
A/I	0.1864	likely_benign	0.2093	benign	-0.354	Destabilizing	0.098	N	0.473	neutral	None	None	None	None	N
A/K	0.648	likely_pathogenic	0.669	pathogenic	-1.471	Destabilizing	0.008	N	0.283	neutral	None	None	None	None	N
A/L	0.1858	likely_benign	0.1944	benign	-0.354	Destabilizing	0.116	N	0.437	neutral	None	None	None	None	N
A/M	0.2401	likely_benign	0.2611	benign	-0.243	Destabilizing	0.69	D	0.53	neutral	None	None	None	None	N
A/N	0.5251	ambiguous	0.5093	ambiguous	-1.191	Destabilizing	0.69	D	0.549	neutral	None	None	None	None	N
A/P	0.7788	likely_pathogenic	0.7361	pathogenic	-0.527	Destabilizing	0.773	D	0.571	neutral	N	0.513321777	None	None	N
A/Q	0.4853	ambiguous	0.5104	ambiguous	-1.318	Destabilizing	0.69	D	0.559	neutral	None	None	None	None	N
A/R	0.5662	likely_pathogenic	0.577	pathogenic	-1.101	Destabilizing	0.527	D	0.573	neutral	None	None	None	None	N
A/S	0.1406	likely_benign	0.1278	benign	-1.509	Destabilizing	0.193	N	0.4	neutral	N	0.499603118	None	None	N
A/T	0.1016	likely_benign	0.1024	benign	-1.425	Destabilizing	0.324	N	0.408	neutral	N	0.461738164	None	None	N
A/V	0.095	likely_benign	0.1003	benign	-0.527	Destabilizing	0.001	N	0.103	neutral	N	0.355122413	None	None	N
A/W	0.7564	likely_pathogenic	0.7806	pathogenic	-1.412	Destabilizing	0.981	D	0.567	neutral	None	None	None	None	N
A/Y	0.5299	ambiguous	0.5726	pathogenic	-1.009	Destabilizing	0.818	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.