TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22531	67816;67817;67818	chr2:178579606;178579605;178579604	chr2:179444333;179444332;179444331
N2AB	20890	62893;62894;62895	chr2:178579606;178579605;178579604	chr2:179444333;179444332;179444331
N2A	19963	60112;60113;60114	chr2:178579606;178579605;178579604	chr2:179444333;179444332;179444331
N2B	13466	40621;40622;40623	chr2:178579606;178579605;178579604	chr2:179444333;179444332;179444331
Novex-1	13591	40996;40997;40998	chr2:178579606;178579605;178579604	chr2:179444333;179444332;179444331
Novex-2	13658	41197;41198;41199	chr2:178579606;178579605;178579604	chr2:179444333;179444332;179444331
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: Fn3-51
• Domain position: 81
• Structural Position: 117
• Q(SASA): 0.6317
• 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/D	None	None	0.891	N	0.434	0.139	0.284150004643	gnomAD-4.0.0	6.84367E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99651E-07	0	0
E/V	None	None	0.801	N	0.605	0.155	0.334659703779	gnomAD-4.0.0	6.84363E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99649E-07	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	0.0972	likely_benign	0.1084	benign	-0.724	Destabilizing	0.051	N	0.342	neutral	N	0.477861543	None	None	N
E/C	0.5831	likely_pathogenic	0.6326	pathogenic	-0.094	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
E/D	0.1968	likely_benign	0.2302	benign	-0.724	Destabilizing	0.891	D	0.434	neutral	N	0.476053389	None	None	N
E/F	0.4695	ambiguous	0.5649	pathogenic	-0.78	Destabilizing	0.728	D	0.645	neutral	None	None	None	None	N
E/G	0.1506	likely_benign	0.1968	benign	-0.961	Destabilizing	0.801	D	0.608	neutral	N	0.509435244	None	None	N
E/H	0.3659	ambiguous	0.4272	ambiguous	-0.957	Destabilizing	0.949	D	0.579	neutral	None	None	None	None	N
E/I	0.1661	likely_benign	0.1884	benign	-0.114	Destabilizing	0.949	D	0.651	neutral	None	None	None	None	N
E/K	0.1009	likely_benign	0.1225	benign	-0.007	Destabilizing	0.891	D	0.487	neutral	N	0.483230078	None	None	N
E/L	0.1967	likely_benign	0.2371	benign	-0.114	Destabilizing	0.728	D	0.605	neutral	None	None	None	None	N
E/M	0.2648	likely_benign	0.3033	benign	0.334	Stabilizing	0.998	D	0.645	neutral	None	None	None	None	N
E/N	0.2607	likely_benign	0.3205	benign	-0.276	Destabilizing	0.974	D	0.565	neutral	None	None	None	None	N
E/P	0.299	likely_benign	0.2978	benign	-0.297	Destabilizing	0.974	D	0.599	neutral	None	None	None	None	N
E/Q	0.1137	likely_benign	0.1262	benign	-0.272	Destabilizing	0.961	D	0.557	neutral	N	0.443903685	None	None	N
E/R	0.162	likely_benign	0.1944	benign	0.03	Stabilizing	0.974	D	0.563	neutral	None	None	None	None	N
E/S	0.1679	likely_benign	0.2032	benign	-0.502	Destabilizing	0.728	D	0.445	neutral	None	None	None	None	N
E/T	0.1489	likely_benign	0.172	benign	-0.306	Destabilizing	0.842	D	0.562	neutral	None	None	None	None	N
E/V	0.1149	likely_benign	0.128	benign	-0.297	Destabilizing	0.801	D	0.605	neutral	N	0.453368531	None	None	N
E/W	0.7535	likely_pathogenic	0.8283	pathogenic	-0.647	Destabilizing	0.993	D	0.64	neutral	None	None	None	None	N
E/Y	0.4435	ambiguous	0.5401	ambiguous	-0.535	Destabilizing	0.007	N	0.429	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.