TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13849	41770;41771;41772	chr2:178636026;178636025;178636024	chr2:179500753;179500752;179500751
N2AB	12208	36847;36848;36849	chr2:178636026;178636025;178636024	chr2:179500753;179500752;179500751
N2A	11281	34066;34067;34068	chr2:178636026;178636025;178636024	chr2:179500753;179500752;179500751
N2B	4784	14575;14576;14577	chr2:178636026;178636025;178636024	chr2:179500753;179500752;179500751
Novex-1	4909	14950;14951;14952	chr2:178636026;178636025;178636024	chr2:179500753;179500752;179500751
Novex-2	4976	15151;15152;15153	chr2:178636026;178636025;178636024	chr2:179500753;179500752;179500751
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-88
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3128
• 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
T/I	rs759603723	-0.063	0.27	N	0.421	0.068	0.176091768786	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/I	rs759603723	-0.063	0.27	N	0.421	0.068	0.176091768786	gnomAD-4.0.0	1.59286E-06	None	None	None	None	N	None	0	2.28728E-05	None	0	0	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
T/A	0.1532	likely_benign	0.1547	benign	-1.059	Destabilizing	0.01	N	0.186	neutral	N	0.353146622	None	None	N
T/C	0.5122	ambiguous	0.52	ambiguous	-0.633	Destabilizing	0.995	D	0.453	neutral	None	None	None	None	N
T/D	0.536	ambiguous	0.5776	pathogenic	-0.487	Destabilizing	0.543	D	0.536	neutral	None	None	None	None	N
T/E	0.4337	ambiguous	0.4785	ambiguous	-0.503	Destabilizing	0.007	N	0.318	neutral	None	None	None	None	N
T/F	0.3333	likely_benign	0.3695	ambiguous	-1.367	Destabilizing	0.893	D	0.569	neutral	None	None	None	None	N
T/G	0.5527	ambiguous	0.558	ambiguous	-1.274	Destabilizing	0.704	D	0.471	neutral	None	None	None	None	N
T/H	0.3433	ambiguous	0.3681	ambiguous	-1.625	Destabilizing	0.944	D	0.535	neutral	None	None	None	None	N
T/I	0.1433	likely_benign	0.1601	benign	-0.578	Destabilizing	0.27	N	0.421	neutral	N	0.344972003	None	None	N
T/K	0.2701	likely_benign	0.2904	benign	-0.739	Destabilizing	0.473	N	0.541	neutral	N	0.345530237	None	None	N
T/L	0.1237	likely_benign	0.1319	benign	-0.578	Destabilizing	0.007	N	0.3	neutral	None	None	None	None	N
T/M	0.1104	likely_benign	0.1146	benign	-0.048	Destabilizing	0.893	D	0.473	neutral	None	None	None	None	N
T/N	0.1431	likely_benign	0.1475	benign	-0.69	Destabilizing	0.704	D	0.476	neutral	None	None	None	None	N
T/P	0.4157	ambiguous	0.3616	ambiguous	-0.709	Destabilizing	0.927	D	0.555	neutral	N	0.370169183	None	None	N
T/Q	0.3132	likely_benign	0.3286	benign	-0.963	Destabilizing	0.807	D	0.538	neutral	None	None	None	None	N
T/R	0.2286	likely_benign	0.254	benign	-0.448	Destabilizing	0.863	D	0.551	neutral	N	0.353140419	None	None	N
T/S	0.1967	likely_benign	0.2078	benign	-0.977	Destabilizing	0.065	N	0.23	neutral	N	0.348731656	None	None	N
T/V	0.1321	likely_benign	0.1458	benign	-0.709	Destabilizing	0.003	N	0.186	neutral	None	None	None	None	N
T/W	0.7393	likely_pathogenic	0.7644	pathogenic	-1.249	Destabilizing	0.995	D	0.608	neutral	None	None	None	None	N
T/Y	0.3643	ambiguous	0.3781	ambiguous	-1.01	Destabilizing	0.981	D	0.562	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.