TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4798	14617;14618;14619	chr2:178736054;178736053;178736052	chr2:179600781;179600780;179600779
N2AB	4481	13666;13667;13668	chr2:178736054;178736053;178736052	chr2:179600781;179600780;179600779
N2A	3554	10885;10886;10887	chr2:178736054;178736053;178736052	chr2:179600781;179600780;179600779
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-31
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.8589
• Predicted PPI site: I

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
L/F	rs2081388048	None	None	D	0.152	0.235	0.287603790349	gnomAD-4.0.0	1.65128E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.95412E-06	0	0
L/P	None	None	None	D	0.283	0.233	0.479818277033	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
L/A	0.2016	likely_benign	0.1948	benign	-0.439	Destabilizing	0.016	N	0.277	neutral	None	None	None	None	I
L/C	0.3205	likely_benign	0.3122	benign	-0.59	Destabilizing	0.676	D	0.234	neutral	None	None	None	None	I
L/D	0.5287	ambiguous	0.4918	ambiguous	0.326	Stabilizing	0.356	N	0.323	neutral	None	None	None	None	I
L/E	0.306	likely_benign	0.2897	benign	0.24	Stabilizing	0.072	N	0.333	neutral	None	None	None	None	I
L/F	0.0714	likely_benign	0.0702	benign	-0.463	Destabilizing	None	N	0.152	neutral	D	0.528361718	None	None	I
L/G	0.4409	ambiguous	0.4149	ambiguous	-0.592	Destabilizing	0.072	N	0.351	neutral	None	None	None	None	I
L/H	0.1253	likely_benign	0.1139	benign	0.056	Stabilizing	0.171	N	0.249	neutral	N	0.497773196	None	None	I
L/I	0.0634	likely_benign	0.0642	benign	-0.164	Destabilizing	0.004	N	0.218	neutral	N	0.349772382	None	None	I
L/K	0.2676	likely_benign	0.2533	benign	-0.083	Destabilizing	0.038	N	0.321	neutral	None	None	None	None	I
L/M	0.1246	likely_benign	0.1279	benign	-0.238	Destabilizing	0.214	N	0.315	neutral	None	None	None	None	I
L/N	0.2655	likely_benign	0.2348	benign	0.071	Stabilizing	0.214	N	0.315	neutral	None	None	None	None	I
L/P	0.6036	likely_pathogenic	0.5499	ambiguous	-0.222	Destabilizing	None	N	0.283	neutral	D	0.592554565	None	None	I
L/Q	0.1283	likely_benign	0.1202	benign	-0.115	Destabilizing	0.214	N	0.289	neutral	None	None	None	None	I
L/R	0.1609	likely_benign	0.1493	benign	0.365	Stabilizing	None	N	0.244	neutral	N	0.457000484	None	None	I
L/S	0.1699	likely_benign	0.1701	benign	-0.446	Destabilizing	0.072	N	0.348	neutral	None	None	None	None	I
L/T	0.1591	likely_benign	0.1591	benign	-0.42	Destabilizing	0.038	N	0.293	neutral	None	None	None	None	I
L/V	0.0718	likely_benign	0.0725	benign	-0.222	Destabilizing	None	N	0.119	neutral	N	0.439920088	None	None	I
L/W	0.1613	likely_benign	0.1676	benign	-0.485	Destabilizing	0.676	D	0.235	neutral	None	None	None	None	I
L/Y	0.149	likely_benign	0.1364	benign	-0.206	Destabilizing	None	N	0.17	neutral	None	None	None	None	I

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.