TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18354	55285;55286;55287	chr2:178602342;178602341;178602340	chr2:179467069;179467068;179467067
N2AB	16713	50362;50363;50364	chr2:178602342;178602341;178602340	chr2:179467069;179467068;179467067
N2A	15786	47581;47582;47583	chr2:178602342;178602341;178602340	chr2:179467069;179467068;179467067
N2B	9289	28090;28091;28092	chr2:178602342;178602341;178602340	chr2:179467069;179467068;179467067
Novex-1	9414	28465;28466;28467	chr2:178602342;178602341;178602340	chr2:179467069;179467068;179467067
Novex-2	9481	28666;28667;28668	chr2:178602342;178602341;178602340	chr2:179467069;179467068;179467067
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: Fn3-21
• Domain position: 83
• Structural Position: 113
• Q(SASA): 0.4693
• 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/G	None	None	0.09	N	0.471	0.104	0.247872288689	gnomAD-4.0.0	1.59318E-06	None	None	None	None	N	None	5.67279E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs1559697777	None	0.324	N	0.339	0.096	0.234412748748	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs1559697777	None	0.324	N	0.339	0.096	0.234412748748	gnomAD-4.0.0	3.84745E-06	None	None	None	None	N	None	1.69285E-05	0	None	0	0	None	0	0	4.7912E-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	0.0873	likely_benign	0.0868	benign	-0.122	Destabilizing	0.001	N	0.135	neutral	N	0.42454992	None	None	N
E/C	0.6988	likely_pathogenic	0.7268	pathogenic	0.146	Stabilizing	0.944	D	0.434	neutral	None	None	None	None	N
E/D	0.0941	likely_benign	0.0934	benign	-0.194	Destabilizing	0.001	N	0.068	neutral	N	0.472381153	None	None	N
E/F	0.5886	likely_pathogenic	0.6065	pathogenic	-0.187	Destabilizing	0.818	D	0.46	neutral	None	None	None	None	N
E/G	0.1324	likely_benign	0.1316	benign	-0.261	Destabilizing	0.09	N	0.471	neutral	N	0.501178333	None	None	N
E/H	0.3493	ambiguous	0.3641	ambiguous	0.159	Stabilizing	0.932	D	0.315	neutral	None	None	None	None	N
E/I	0.2276	likely_benign	0.2322	benign	0.188	Stabilizing	0.69	D	0.479	neutral	None	None	None	None	N
E/K	0.1159	likely_benign	0.1202	benign	0.607	Stabilizing	0.324	N	0.327	neutral	N	0.427763584	None	None	N
E/L	0.247	likely_benign	0.2505	benign	0.188	Stabilizing	0.388	N	0.487	neutral	None	None	None	None	N
E/M	0.3162	likely_benign	0.3292	benign	0.213	Stabilizing	0.981	D	0.427	neutral	None	None	None	None	N
E/N	0.165	likely_benign	0.1665	benign	0.368	Stabilizing	0.241	N	0.296	neutral	None	None	None	None	N
E/P	0.4535	ambiguous	0.444	ambiguous	0.104	Stabilizing	0.818	D	0.419	neutral	None	None	None	None	N
E/Q	0.1302	likely_benign	0.1303	benign	0.381	Stabilizing	0.324	N	0.339	neutral	N	0.49383386	None	None	N
E/R	0.1998	likely_benign	0.2083	benign	0.705	Stabilizing	0.69	D	0.307	neutral	None	None	None	None	N
E/S	0.135	likely_benign	0.1356	benign	0.233	Stabilizing	0.008	N	0.151	neutral	None	None	None	None	N
E/T	0.1449	likely_benign	0.1481	benign	0.352	Stabilizing	0.241	N	0.413	neutral	None	None	None	None	N
E/V	0.1432	likely_benign	0.1445	benign	0.104	Stabilizing	0.193	N	0.459	neutral	N	0.500106472	None	None	N
E/W	0.8088	likely_pathogenic	0.835	pathogenic	-0.124	Destabilizing	0.981	D	0.552	neutral	None	None	None	None	N
E/Y	0.4418	ambiguous	0.4555	ambiguous	0.046	Stabilizing	0.932	D	0.443	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.