TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30891	92896;92897;92898	chr2:178548955;178548954;178548953	chr2:179413682;179413681;179413680
N2AB	29250	87973;87974;87975	chr2:178548955;178548954;178548953	chr2:179413682;179413681;179413680
N2A	28323	85192;85193;85194	chr2:178548955;178548954;178548953	chr2:179413682;179413681;179413680
N2B	21826	65701;65702;65703	chr2:178548955;178548954;178548953	chr2:179413682;179413681;179413680
Novex-1	21951	66076;66077;66078	chr2:178548955;178548954;178548953	chr2:179413682;179413681;179413680
Novex-2	22018	66277;66278;66279	chr2:178548955;178548954;178548953	chr2:179413682;179413681;179413680
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-113
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3872
• 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
E/Q	None	None	0.801	N	0.471	0.193	0.227260227426	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.1246	likely_benign	0.1299	benign	-0.953	Destabilizing	0.625	D	0.416	neutral	N	0.478663393	None	None	N
E/C	0.7746	likely_pathogenic	0.7881	pathogenic	-0.472	Destabilizing	0.998	D	0.618	neutral	None	None	None	None	N
E/D	0.1365	likely_benign	0.1346	benign	-1.046	Destabilizing	0.801	D	0.38	neutral	N	0.46844595	None	None	N
E/F	0.6716	likely_pathogenic	0.6822	pathogenic	-0.427	Destabilizing	0.949	D	0.609	neutral	None	None	None	None	N
E/G	0.1885	likely_benign	0.1942	benign	-1.313	Destabilizing	0.801	D	0.564	neutral	N	0.496540612	None	None	N
E/H	0.4891	ambiguous	0.4924	ambiguous	-0.714	Destabilizing	0.037	N	0.201	neutral	None	None	None	None	N
E/I	0.2613	likely_benign	0.264	benign	0.029	Stabilizing	0.728	D	0.563	neutral	None	None	None	None	N
E/K	0.2019	likely_benign	0.2046	benign	-0.599	Destabilizing	0.801	D	0.405	neutral	N	0.48636917	None	None	N
E/L	0.3218	likely_benign	0.3236	benign	0.029	Stabilizing	0.007	N	0.353	neutral	None	None	None	None	N
E/M	0.3283	likely_benign	0.3422	ambiguous	0.499	Stabilizing	0.949	D	0.603	neutral	None	None	None	None	N
E/N	0.2123	likely_benign	0.2066	benign	-1.049	Destabilizing	0.842	D	0.448	neutral	None	None	None	None	N
E/P	0.5656	likely_pathogenic	0.5313	ambiguous	-0.278	Destabilizing	0.991	D	0.549	neutral	None	None	None	None	N
E/Q	0.1613	likely_benign	0.1664	benign	-0.926	Destabilizing	0.801	D	0.471	neutral	N	0.514806565	None	None	N
E/R	0.347	ambiguous	0.3646	ambiguous	-0.347	Destabilizing	0.949	D	0.457	neutral	None	None	None	None	N
E/S	0.1858	likely_benign	0.1936	benign	-1.375	Destabilizing	0.842	D	0.387	neutral	None	None	None	None	N
E/T	0.1644	likely_benign	0.1689	benign	-1.074	Destabilizing	0.915	D	0.487	neutral	None	None	None	None	N
E/V	0.1601	likely_benign	0.1633	benign	-0.278	Destabilizing	0.669	D	0.496	neutral	N	0.492844082	None	None	N
E/W	0.8801	likely_pathogenic	0.8864	pathogenic	-0.159	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
E/Y	0.5464	ambiguous	0.5591	ambiguous	-0.169	Destabilizing	0.949	D	0.588	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.