TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8251	24976;24977;24978	chr2:178718355;178718354;178718353	chr2:179583082;179583081;179583080
N2AB	7934	24025;24026;24027	chr2:178718355;178718354;178718353	chr2:179583082;179583081;179583080
N2A	7007	21244;21245;21246	chr2:178718355;178718354;178718353	chr2:179583082;179583081;179583080
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-67
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.539
• 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
Q/H	rs1377167368	-0.656	0.001	N	0.159	0.16	0.259761712551	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Q/H	rs1377167368	-0.656	0.001	N	0.159	0.16	0.259761712551	gnomAD-4.0.0	3.42136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49772E-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
Q/A	0.2048	likely_benign	0.1728	benign	-0.3	Destabilizing	0.016	N	0.287	neutral	None	None	None	None	N
Q/C	0.6058	likely_pathogenic	0.5516	ambiguous	0.13	Stabilizing	0.901	D	0.517	neutral	None	None	None	None	N
Q/D	0.3474	ambiguous	0.2986	benign	0.028	Stabilizing	0.036	N	0.212	neutral	None	None	None	None	N
Q/E	0.0739	likely_benign	0.0678	benign	0.03	Stabilizing	None	N	0.124	neutral	N	0.438991803	None	None	N
Q/F	0.6352	likely_pathogenic	0.5701	pathogenic	-0.352	Destabilizing	0.174	N	0.565	neutral	None	None	None	None	N
Q/G	0.2083	likely_benign	0.176	benign	-0.535	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
Q/H	0.1943	likely_benign	0.1716	benign	-0.354	Destabilizing	0.001	N	0.159	neutral	N	0.499640404	None	None	N
Q/I	0.3959	ambiguous	0.3405	ambiguous	0.241	Stabilizing	0.296	N	0.575	neutral	None	None	None	None	N
Q/K	0.064	likely_benign	0.0654	benign	0.016	Stabilizing	0.028	N	0.189	neutral	N	0.431372397	None	None	N
Q/L	0.165	likely_benign	0.1422	benign	0.241	Stabilizing	0.116	N	0.441	neutral	N	0.490620762	None	None	N
Q/M	0.3413	ambiguous	0.3062	benign	0.473	Stabilizing	0.901	D	0.368	neutral	None	None	None	None	N
Q/N	0.2501	likely_benign	0.2227	benign	-0.356	Destabilizing	0.148	N	0.269	neutral	None	None	None	None	N
Q/P	0.3887	ambiguous	0.3615	ambiguous	0.09	Stabilizing	0.391	N	0.489	neutral	D	0.529269877	None	None	N
Q/R	0.0739	likely_benign	0.0725	benign	0.178	Stabilizing	None	N	0.139	neutral	N	0.456580273	None	None	N
Q/S	0.2073	likely_benign	0.1843	benign	-0.39	Destabilizing	0.007	N	0.123	neutral	None	None	None	None	N
Q/T	0.1724	likely_benign	0.1523	benign	-0.217	Destabilizing	0.002	N	0.165	neutral	None	None	None	None	N
Q/V	0.2608	likely_benign	0.2232	benign	0.09	Stabilizing	0.148	N	0.458	neutral	None	None	None	None	N
Q/W	0.4695	ambiguous	0.4116	ambiguous	-0.284	Destabilizing	0.901	D	0.505	neutral	None	None	None	None	N
Q/Y	0.4094	ambiguous	0.3515	ambiguous	-0.048	Destabilizing	0.002	N	0.187	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.