TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9154	27685;27686;27687	chr2:178712462;178712461;178712460	chr2:179577189;179577188;179577187
N2AB	8837	26734;26735;26736	chr2:178712462;178712461;178712460	chr2:179577189;179577188;179577187
N2A	7910	23953;23954;23955	chr2:178712462;178712461;178712460	chr2:179577189;179577188;179577187
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-77
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.6723
• 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
P/L	None	None	0.012	N	0.308	0.159	0.56713362702	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
P/S	None	None	0.012	N	0.336	0.07	0.245101548738	gnomAD-4.0.0	6.84188E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99446E-07	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
P/A	0.0558	likely_benign	0.0566	benign	-0.323	Destabilizing	None	N	0.147	neutral	N	0.456174841	None	None	N
P/C	0.3552	ambiguous	0.3256	benign	-0.575	Destabilizing	0.356	N	0.368	neutral	None	None	None	None	N
P/D	0.2687	likely_benign	0.2637	benign	-0.262	Destabilizing	0.072	N	0.297	neutral	None	None	None	None	N
P/E	0.1539	likely_benign	0.156	benign	-0.389	Destabilizing	0.016	N	0.317	neutral	None	None	None	None	N
P/F	0.2706	likely_benign	0.2557	benign	-0.689	Destabilizing	0.356	N	0.407	neutral	None	None	None	None	N
P/G	0.1936	likely_benign	0.1831	benign	-0.419	Destabilizing	0.016	N	0.278	neutral	None	None	None	None	N
P/H	0.1051	likely_benign	0.1082	benign	-0.091	Destabilizing	None	N	0.231	neutral	N	0.50873989	None	None	N
P/I	0.1749	likely_benign	0.1669	benign	-0.227	Destabilizing	0.072	N	0.411	neutral	None	None	None	None	N
P/K	0.1572	likely_benign	0.1513	benign	-0.324	Destabilizing	0.016	N	0.299	neutral	None	None	None	None	N
P/L	0.0839	likely_benign	0.0852	benign	-0.227	Destabilizing	0.012	N	0.308	neutral	N	0.509913326	None	None	N
P/M	0.2087	likely_benign	0.196	benign	-0.322	Destabilizing	0.356	N	0.36	neutral	None	None	None	None	N
P/N	0.1792	likely_benign	0.1673	benign	-0.044	Destabilizing	0.072	N	0.363	neutral	None	None	None	None	N
P/Q	0.0832	likely_benign	0.0843	benign	-0.291	Destabilizing	None	N	0.166	neutral	None	None	None	None	N
P/R	0.1056	likely_benign	0.1094	benign	0.152	Stabilizing	0.029	N	0.363	neutral	N	0.52124504	None	None	N
P/S	0.0786	likely_benign	0.0759	benign	-0.361	Destabilizing	0.012	N	0.336	neutral	N	0.454286542	None	None	N
P/T	0.0715	likely_benign	0.0708	benign	-0.391	Destabilizing	0.012	N	0.289	neutral	N	0.490018056	None	None	N
P/V	0.1289	likely_benign	0.125	benign	-0.226	Destabilizing	0.016	N	0.282	neutral	None	None	None	None	N
P/W	0.3891	ambiguous	0.3879	ambiguous	-0.772	Destabilizing	0.864	D	0.376	neutral	None	None	None	None	N
P/Y	0.2306	likely_benign	0.2248	benign	-0.461	Destabilizing	0.214	N	0.453	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.