TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35610	107053;107054;107055	chr2:178528923;178528922;178528921	chr2:179393650;179393649;179393648
N2AB	33969	102130;102131;102132	chr2:178528923;178528922;178528921	chr2:179393650;179393649;179393648
N2A	33042	99349;99350;99351	chr2:178528923;178528922;178528921	chr2:179393650;179393649;179393648
N2B	26545	79858;79859;79860	chr2:178528923;178528922;178528921	chr2:179393650;179393649;179393648
Novex-1	26670	80233;80234;80235	chr2:178528923;178528922;178528921	chr2:179393650;179393649;179393648
Novex-2	26737	80434;80435;80436	chr2:178528923;178528922;178528921	chr2:179393650;179393649;179393648
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-167
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.4675
• 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	rs753984036	-0.123	0.684	N	0.392	0.312	0.273503213844	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	1.65399E-04
K/E	rs753984036	-0.123	0.684	N	0.392	0.312	0.273503213844	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/E	rs753984036	-0.123	0.684	N	0.392	0.312	0.273503213844	gnomAD-4.0.0	3.53176E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.66144E-05	0	3.20184E-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	0.5095	ambiguous	0.4348	ambiguous	-0.124	Destabilizing	0.373	N	0.385	neutral	None	None	None	None	N
K/C	0.9134	likely_pathogenic	0.8859	pathogenic	-0.674	Destabilizing	0.996	D	0.429	neutral	None	None	None	None	N
K/D	0.7401	likely_pathogenic	0.68	pathogenic	-0.324	Destabilizing	0.742	D	0.401	neutral	None	None	None	None	N
K/E	0.2464	likely_benign	0.2073	benign	-0.321	Destabilizing	0.684	D	0.392	neutral	N	0.472989733	None	None	N
K/F	0.8959	likely_pathogenic	0.8604	pathogenic	-0.505	Destabilizing	0.953	D	0.417	neutral	None	None	None	None	N
K/G	0.6814	likely_pathogenic	0.6146	pathogenic	-0.238	Destabilizing	0.742	D	0.383	neutral	None	None	None	None	N
K/H	0.4805	ambiguous	0.4403	ambiguous	-0.269	Destabilizing	0.953	D	0.393	neutral	None	None	None	None	N
K/I	0.5096	ambiguous	0.4305	ambiguous	0.099	Stabilizing	0.884	D	0.433	neutral	N	0.4743766	None	None	N
K/L	0.5124	ambiguous	0.4421	ambiguous	0.099	Stabilizing	0.59	D	0.396	neutral	None	None	None	None	N
K/M	0.3616	ambiguous	0.2957	benign	-0.385	Destabilizing	0.953	D	0.393	neutral	None	None	None	None	N
K/N	0.5487	ambiguous	0.4915	ambiguous	-0.245	Destabilizing	0.684	D	0.381	neutral	N	0.474549958	None	None	N
K/P	0.8216	likely_pathogenic	0.7723	pathogenic	0.046	Stabilizing	0.953	D	0.414	neutral	None	None	None	None	N
K/Q	0.1945	likely_benign	0.1773	benign	-0.309	Destabilizing	0.684	D	0.422	neutral	N	0.474029883	None	None	N
K/R	0.1204	likely_benign	0.1136	benign	-0.159	Destabilizing	0.003	N	0.093	neutral	N	0.455617481	None	None	N
K/S	0.5731	likely_pathogenic	0.5103	ambiguous	-0.563	Destabilizing	0.59	D	0.369	neutral	None	None	None	None	N
K/T	0.2441	likely_benign	0.2035	benign	-0.444	Destabilizing	0.003	N	0.181	neutral	N	0.453710539	None	None	N
K/V	0.5159	ambiguous	0.4369	ambiguous	0.046	Stabilizing	0.59	D	0.411	neutral	None	None	None	None	N
K/W	0.9215	likely_pathogenic	0.8961	pathogenic	-0.647	Destabilizing	0.996	D	0.543	neutral	None	None	None	None	N
K/Y	0.8297	likely_pathogenic	0.7842	pathogenic	-0.299	Destabilizing	0.984	D	0.385	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.