TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17005	51238;51239;51240	chr2:178611116;178611115;178611114	chr2:179475843;179475842;179475841
N2AB	15364	46315;46316;46317	chr2:178611116;178611115;178611114	chr2:179475843;179475842;179475841
N2A	14437	43534;43535;43536	chr2:178611116;178611115;178611114	chr2:179475843;179475842;179475841
N2B	7940	24043;24044;24045	chr2:178611116;178611115;178611114	chr2:179475843;179475842;179475841
Novex-1	8065	24418;24419;24420	chr2:178611116;178611115;178611114	chr2:179475843;179475842;179475841
Novex-2	8132	24619;24620;24621	chr2:178611116;178611115;178611114	chr2:179475843;179475842;179475841
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-111
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.5086
• 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
N/K	rs752077995	None	None	N	0.252	0.165	0.0297737177859	gnomAD-4.0.0	2.73825E-06	None	None	None	None	N	None	5.98552E-05	0	None	0	0	None	0	0	8.99831E-07	0	1.65793E-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
N/A	0.1521	likely_benign	0.156	benign	-0.454	Destabilizing	None	N	0.442	neutral	None	None	None	None	N
N/C	0.1959	likely_benign	0.1859	benign	0.368	Stabilizing	0.676	D	0.655	neutral	None	None	None	None	N
N/D	0.1492	likely_benign	0.1604	benign	-0.053	Destabilizing	0.012	N	0.447	neutral	N	0.497894614	None	None	N
N/E	0.2887	likely_benign	0.3058	benign	-0.04	Destabilizing	0.016	N	0.459	neutral	None	None	None	None	N
N/F	0.4616	ambiguous	0.4746	ambiguous	-0.579	Destabilizing	0.356	N	0.665	neutral	None	None	None	None	N
N/G	0.2208	likely_benign	0.223	benign	-0.708	Destabilizing	0.016	N	0.411	neutral	None	None	None	None	N
N/H	0.1167	likely_benign	0.1217	benign	-0.727	Destabilizing	0.295	N	0.605	neutral	N	0.51091066	None	None	N
N/I	0.1613	likely_benign	0.1638	benign	0.144	Stabilizing	0.171	N	0.663	neutral	N	0.503717841	None	None	N
N/K	0.2094	likely_benign	0.2396	benign	-0.002	Destabilizing	None	N	0.252	neutral	N	0.488956044	None	None	N
N/L	0.1914	likely_benign	0.1902	benign	0.144	Stabilizing	0.072	N	0.611	neutral	None	None	None	None	N
N/M	0.2237	likely_benign	0.2202	benign	0.576	Stabilizing	0.628	D	0.657	neutral	None	None	None	None	N
N/P	0.502	ambiguous	0.5241	ambiguous	-0.026	Destabilizing	0.072	N	0.657	neutral	None	None	None	None	N
N/Q	0.2543	likely_benign	0.2657	benign	-0.49	Destabilizing	0.038	N	0.559	neutral	None	None	None	None	N
N/R	0.2615	likely_benign	0.2825	benign	-0.028	Destabilizing	0.038	N	0.483	neutral	None	None	None	None	N
N/S	0.0724	likely_benign	0.0678	benign	-0.336	Destabilizing	None	N	0.254	neutral	N	0.461946031	None	None	N
N/T	0.0764	likely_benign	0.0742	benign	-0.154	Destabilizing	0.012	N	0.457	neutral	N	0.477026478	None	None	N
N/V	0.1667	likely_benign	0.1675	benign	-0.026	Destabilizing	0.072	N	0.613	neutral	None	None	None	None	N
N/W	0.6378	likely_pathogenic	0.6319	pathogenic	-0.475	Destabilizing	0.864	D	0.677	prob.neutral	None	None	None	None	N
N/Y	0.1271	likely_benign	0.1324	benign	-0.234	Destabilizing	0.295	N	0.663	neutral	N	0.510373586	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.