TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19728	59407;59408;59409	chr2:178592937;178592936;178592935	chr2:179457664;179457663;179457662
N2AB	18087	54484;54485;54486	chr2:178592937;178592936;178592935	chr2:179457664;179457663;179457662
N2A	17160	51703;51704;51705	chr2:178592937;178592936;178592935	chr2:179457664;179457663;179457662
N2B	10663	32212;32213;32214	chr2:178592937;178592936;178592935	chr2:179457664;179457663;179457662
Novex-1	10788	32587;32588;32589	chr2:178592937;178592936;178592935	chr2:179457664;179457663;179457662
Novex-2	10855	32788;32789;32790	chr2:178592937;178592936;178592935	chr2:179457664;179457663;179457662
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-31
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.6937
• 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/K	None	None	None	N	0.175	0.119	0.0482279557977	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.2673	likely_benign	0.2176	benign	-0.306	Destabilizing	0.016	N	0.377	neutral	None	None	None	None	N
R/C	0.139	likely_benign	0.1425	benign	-0.387	Destabilizing	0.864	D	0.382	neutral	None	None	None	None	N
R/D	0.5421	ambiguous	0.4848	ambiguous	-0.146	Destabilizing	0.072	N	0.424	neutral	None	None	None	None	N
R/E	0.2065	likely_benign	0.1727	benign	0.005	Stabilizing	0.016	N	0.395	neutral	None	None	None	None	N
R/F	0.3287	likely_benign	0.3179	benign	-0.032	Destabilizing	0.628	D	0.401	neutral	None	None	None	None	N
R/G	0.2285	likely_benign	0.1753	benign	-0.617	Destabilizing	0.024	N	0.421	neutral	N	0.496759522	None	None	N
R/H	0.0884	likely_benign	0.091	benign	-1.102	Destabilizing	0.356	N	0.451	neutral	None	None	None	None	N
R/I	0.1124	likely_benign	0.0985	benign	0.526	Stabilizing	0.171	N	0.409	neutral	N	0.409793899	None	None	N
R/K	0.0611	likely_benign	0.0547	benign	-0.272	Destabilizing	None	N	0.175	neutral	N	0.414159568	None	None	N
R/L	0.1282	likely_benign	0.1162	benign	0.526	Stabilizing	0.031	N	0.421	neutral	None	None	None	None	N
R/M	0.1368	likely_benign	0.1154	benign	-0.141	Destabilizing	0.628	D	0.41	neutral	None	None	None	None	N
R/N	0.337	likely_benign	0.2878	benign	-0.146	Destabilizing	0.072	N	0.355	neutral	None	None	None	None	N
R/P	0.8629	likely_pathogenic	0.8024	pathogenic	0.27	Stabilizing	0.136	N	0.417	neutral	None	None	None	None	N
R/Q	0.0753	likely_benign	0.0719	benign	-0.107	Destabilizing	0.038	N	0.378	neutral	None	None	None	None	N
R/S	0.2927	likely_benign	0.2401	benign	-0.597	Destabilizing	0.012	N	0.411	neutral	N	0.422453765	None	None	N
R/T	0.1298	likely_benign	0.1039	benign	-0.259	Destabilizing	None	N	0.244	neutral	N	0.426686148	None	None	N
R/V	0.1492	likely_benign	0.1284	benign	0.27	Stabilizing	0.072	N	0.414	neutral	None	None	None	None	N
R/W	0.1766	likely_benign	0.1611	benign	0.1	Stabilizing	0.864	D	0.394	neutral	None	None	None	None	N
R/Y	0.2895	likely_benign	0.2812	benign	0.41	Stabilizing	0.356	N	0.413	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.