TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8568	25927;25928;25929	chr2:178715712;178715711;178715710	chr2:179580439;179580438;179580437
N2AB	8251	24976;24977;24978	chr2:178715712;178715711;178715710	chr2:179580439;179580438;179580437
N2A	7324	22195;22196;22197	chr2:178715712;178715711;178715710	chr2:179580439;179580438;179580437
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-71
• Domain position: 20
• Structural Position: 29
• Q(SASA): 0.5612
• 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
R/M	None	None	0.97	N	0.62	0.217	0.254244900254	gnomAD-4.0.0	1.61428E-06	None	None	None	None	N	None	0	0	None	0	2.79861E-05	None	0	0	0	0	0
R/S	None	None	0.642	N	0.547	0.158	0.117506650769	gnomAD-4.0.0	6.88015E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66478E-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
R/A	0.2505	likely_benign	0.2478	benign	-0.938	Destabilizing	0.495	N	0.54	neutral	None	None	None	None	N
R/C	0.162	likely_benign	0.1598	benign	-0.975	Destabilizing	0.997	D	0.647	neutral	None	None	None	None	N
R/D	0.5538	ambiguous	0.5467	ambiguous	-0.013	Destabilizing	0.826	D	0.588	neutral	None	None	None	None	N
R/E	0.2679	likely_benign	0.2643	benign	0.151	Stabilizing	0.417	N	0.609	neutral	None	None	None	None	N
R/F	0.4108	ambiguous	0.3987	ambiguous	-0.581	Destabilizing	0.931	D	0.649	neutral	None	None	None	None	N
R/G	0.2036	likely_benign	0.1988	benign	-1.266	Destabilizing	0.782	D	0.558	neutral	N	0.498497216	None	None	N
R/H	0.082	likely_benign	0.0811	benign	-1.425	Destabilizing	0.933	D	0.627	neutral	None	None	None	None	N
R/I	0.1713	likely_benign	0.174	benign	-0.042	Destabilizing	0.874	D	0.649	neutral	None	None	None	None	N
R/K	0.0957	likely_benign	0.0972	benign	-0.716	Destabilizing	0.081	N	0.611	neutral	N	0.446087481	None	None	N
R/L	0.181	likely_benign	0.1806	benign	-0.042	Destabilizing	0.497	N	0.555	neutral	None	None	None	None	N
R/M	0.2063	likely_benign	0.2028	benign	-0.571	Destabilizing	0.97	D	0.62	neutral	N	0.46614982	None	None	N
R/N	0.383	ambiguous	0.3879	ambiguous	-0.462	Destabilizing	0.826	D	0.589	neutral	None	None	None	None	N
R/P	0.8149	likely_pathogenic	0.8107	pathogenic	-0.321	Destabilizing	0.971	D	0.62	neutral	None	None	None	None	N
R/Q	0.0906	likely_benign	0.0906	benign	-0.505	Destabilizing	0.24	N	0.455	neutral	None	None	None	None	N
R/S	0.259	likely_benign	0.2583	benign	-1.262	Destabilizing	0.642	D	0.547	neutral	N	0.46896434	None	None	N
R/T	0.1087	likely_benign	0.1063	benign	-0.896	Destabilizing	0.02	N	0.379	neutral	N	0.442679029	None	None	N
R/V	0.2082	likely_benign	0.2059	benign	-0.321	Destabilizing	0.417	N	0.585	neutral	None	None	None	None	N
R/W	0.1528	likely_benign	0.1464	benign	-0.216	Destabilizing	0.998	D	0.681	prob.neutral	N	0.498750706	None	None	N
R/Y	0.2937	likely_benign	0.2823	benign	0.028	Stabilizing	0.976	D	0.63	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.