TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15625	47098;47099;47100	chr2:178618677;178618676;178618675	chr2:179483404;179483403;179483402
N2AB	13984	42175;42176;42177	chr2:178618677;178618676;178618675	chr2:179483404;179483403;179483402
N2A	13057	39394;39395;39396	chr2:178618677;178618676;178618675	chr2:179483404;179483403;179483402
N2B	6560	19903;19904;19905	chr2:178618677;178618676;178618675	chr2:179483404;179483403;179483402
Novex-1	6685	20278;20279;20280	chr2:178618677;178618676;178618675	chr2:179483404;179483403;179483402
Novex-2	6752	20479;20480;20481	chr2:178618677;178618676;178618675	chr2:179483404;179483403;179483402
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-108
• Domain position: 58
• Structural Position: 141
• Q(SASA): 0.5078
• 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
L/S	None	None	None	N	0.22	0.066	0.324161360171	gnomAD-4.0.0	1.59468E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03251E-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	0.0795	likely_benign	0.0817	benign	-0.575	Destabilizing	0.007	N	0.293	neutral	None	None	None	None	N
L/C	0.2632	likely_benign	0.3186	benign	-0.65	Destabilizing	0.356	N	0.375	neutral	None	None	None	None	N
L/D	0.2227	likely_benign	0.2594	benign	-0.305	Destabilizing	0.038	N	0.459	neutral	None	None	None	None	N
L/E	0.1337	likely_benign	0.1516	benign	-0.397	Destabilizing	0.016	N	0.444	neutral	None	None	None	None	N
L/F	0.0688	likely_benign	0.0893	benign	-0.591	Destabilizing	0.029	N	0.283	neutral	N	0.48601087	None	None	N
L/G	0.1688	likely_benign	0.1892	benign	-0.726	Destabilizing	0.016	N	0.438	neutral	None	None	None	None	N
L/H	0.0963	likely_benign	0.1121	benign	0.002	Stabilizing	0.214	N	0.417	neutral	None	None	None	None	N
L/I	0.0667	likely_benign	0.0729	benign	-0.298	Destabilizing	0.012	N	0.221	neutral	N	0.48601087	None	None	N
L/K	0.1099	likely_benign	0.1136	benign	-0.395	Destabilizing	None	N	0.167	neutral	None	None	None	None	N
L/M	0.0778	likely_benign	0.0888	benign	-0.452	Destabilizing	0.356	N	0.318	neutral	None	None	None	None	N
L/N	0.1217	likely_benign	0.1167	benign	-0.201	Destabilizing	0.038	N	0.462	neutral	None	None	None	None	N
L/P	0.0771	likely_benign	0.0845	benign	-0.358	Destabilizing	0.072	N	0.458	neutral	None	None	None	None	N
L/Q	0.0755	likely_benign	0.0793	benign	-0.426	Destabilizing	0.072	N	0.444	neutral	None	None	None	None	N
L/R	0.0987	likely_benign	0.1116	benign	0.17	Stabilizing	0.038	N	0.443	neutral	None	None	None	None	N
L/S	0.0774	likely_benign	0.081	benign	-0.612	Destabilizing	None	N	0.22	neutral	N	0.481122547	None	None	N
L/T	0.0697	likely_benign	0.072	benign	-0.6	Destabilizing	None	N	0.163	neutral	None	None	None	None	N
L/V	0.0658	likely_benign	0.0706	benign	-0.358	Destabilizing	None	N	0.129	neutral	N	0.46630899	None	None	N
L/W	0.1242	likely_benign	0.1613	benign	-0.605	Destabilizing	0.676	D	0.387	neutral	None	None	None	None	N
L/Y	0.1431	likely_benign	0.1823	benign	-0.368	Destabilizing	None	N	0.205	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.