TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32425	97498;97499;97500	chr2:178542483;178542482;178542481	chr2:179407210;179407209;179407208
N2AB	30784	92575;92576;92577	chr2:178542483;178542482;178542481	chr2:179407210;179407209;179407208
N2A	29857	89794;89795;89796	chr2:178542483;178542482;178542481	chr2:179407210;179407209;179407208
N2B	23360	70303;70304;70305	chr2:178542483;178542482;178542481	chr2:179407210;179407209;179407208
Novex-1	23485	70678;70679;70680	chr2:178542483;178542482;178542481	chr2:179407210;179407209;179407208
Novex-2	23552	70879;70880;70881	chr2:178542483;178542482;178542481	chr2:179407210;179407209;179407208
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: Fn3-124
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.6844
• 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	0.722	N	0.531	0.092	0.351614576976	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43316E-05	0
E/K	rs1169300714	0.654	0.565	N	0.579	0.176	0.298056030225	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs1169300714	0.654	0.565	N	0.579	0.176	0.298056030225	gnomAD-4.0.0	1.59306E-06	None	None	None	None	N	None	5.65803E-05	0	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
E/A	0.0979	likely_benign	0.1011	benign	-0.121	Destabilizing	0.565	D	0.549	neutral	N	0.465185822	None	None	N
E/C	0.681	likely_pathogenic	0.6502	pathogenic	-0.117	Destabilizing	0.996	D	0.662	neutral	None	None	None	None	N
E/D	0.138	likely_benign	0.1308	benign	-0.281	Destabilizing	0.722	D	0.531	neutral	N	0.500087829	None	None	N
E/F	0.5845	likely_pathogenic	0.5448	ambiguous	-0.086	Destabilizing	0.923	D	0.617	neutral	None	None	None	None	N
E/G	0.1582	likely_benign	0.144	benign	-0.263	Destabilizing	0.901	D	0.505	neutral	N	0.49143106	None	None	N
E/H	0.3336	likely_benign	0.3112	benign	0.417	Stabilizing	0.979	D	0.521	neutral	None	None	None	None	N
E/I	0.1684	likely_benign	0.1684	benign	0.201	Stabilizing	0.858	D	0.616	neutral	None	None	None	None	N
E/K	0.1048	likely_benign	0.1003	benign	0.462	Stabilizing	0.565	D	0.579	neutral	N	0.462068159	None	None	N
E/L	0.1824	likely_benign	0.1825	benign	0.201	Stabilizing	0.024	N	0.397	neutral	None	None	None	None	N
E/M	0.2649	likely_benign	0.2615	benign	0.064	Stabilizing	0.923	D	0.587	neutral	None	None	None	None	N
E/N	0.2162	likely_benign	0.1998	benign	0.149	Stabilizing	0.923	D	0.501	neutral	None	None	None	None	N
E/P	0.3715	ambiguous	0.3996	ambiguous	0.112	Stabilizing	0.961	D	0.519	neutral	None	None	None	None	N
E/Q	0.1033	likely_benign	0.1006	benign	0.174	Stabilizing	0.034	N	0.172	neutral	N	0.505995081	None	None	N
E/R	0.1782	likely_benign	0.1674	benign	0.684	Stabilizing	0.858	D	0.49	neutral	None	None	None	None	N
E/S	0.1512	likely_benign	0.1481	benign	0.019	Stabilizing	0.633	D	0.56	neutral	None	None	None	None	N
E/T	0.1454	likely_benign	0.1456	benign	0.144	Stabilizing	0.923	D	0.504	neutral	None	None	None	None	N
E/V	0.1088	likely_benign	0.11	benign	0.112	Stabilizing	0.565	D	0.508	neutral	N	0.489102831	None	None	N
E/W	0.8336	likely_pathogenic	0.8008	pathogenic	0.003	Stabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	N
E/Y	0.4862	ambiguous	0.4441	ambiguous	0.149	Stabilizing	0.961	D	0.589	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.