TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7049	21370;21371;21372	chr2:178724114;178724113;178724112	chr2:179588841;179588840;179588839
N2AB	6732	20419;20420;20421	chr2:178724114;178724113;178724112	chr2:179588841;179588840;179588839
N2A	5805	17638;17639;17640	chr2:178724114;178724113;178724112	chr2:179588841;179588840;179588839
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: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-55
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5405
• 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/S	rs2078919390	None	0.425	N	0.401	0.268	0.292787519742	gnomAD-4.0.0	1.36959E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00098E-07	0	1.65854E-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	0.2878	likely_benign	0.2295	benign	-0.816	Destabilizing	0.495	N	0.379	neutral	None	None	None	None	N
R/C	0.219	likely_benign	0.1676	benign	-0.76	Destabilizing	0.995	D	0.362	neutral	None	None	None	None	N
R/D	0.5896	likely_pathogenic	0.5024	ambiguous	0.137	Stabilizing	0.704	D	0.417	neutral	None	None	None	None	N
R/E	0.3021	likely_benign	0.2319	benign	0.263	Stabilizing	0.329	N	0.337	neutral	None	None	None	None	N
R/F	0.4616	ambiguous	0.3822	ambiguous	-0.695	Destabilizing	0.007	N	0.329	neutral	None	None	None	None	N
R/G	0.1879	likely_benign	0.1498	benign	-1.107	Destabilizing	0.425	N	0.429	neutral	N	0.489730054	None	None	N
R/H	0.1164	likely_benign	0.0949	benign	-1.393	Destabilizing	0.981	D	0.385	neutral	None	None	None	None	N
R/I	0.2022	likely_benign	0.1716	benign	-0.038	Destabilizing	0.642	D	0.444	neutral	D	0.529555092	None	None	N
R/K	0.0799	likely_benign	0.075	benign	-0.601	Destabilizing	0.001	N	0.107	neutral	N	0.374980397	None	None	N
R/L	0.1742	likely_benign	0.1418	benign	-0.038	Destabilizing	0.329	N	0.395	neutral	None	None	None	None	N
R/M	0.1887	likely_benign	0.1617	benign	-0.415	Destabilizing	0.981	D	0.399	neutral	None	None	None	None	N
R/N	0.4432	ambiguous	0.3691	ambiguous	-0.176	Destabilizing	0.704	D	0.319	neutral	None	None	None	None	N
R/P	0.2498	likely_benign	0.197	benign	-0.277	Destabilizing	0.828	D	0.441	neutral	None	None	None	None	N
R/Q	0.1029	likely_benign	0.0859	benign	-0.327	Destabilizing	0.704	D	0.334	neutral	None	None	None	None	N
R/S	0.3596	ambiguous	0.2834	benign	-0.987	Destabilizing	0.425	N	0.401	neutral	N	0.478800985	None	None	N
R/T	0.1922	likely_benign	0.1544	benign	-0.674	Destabilizing	0.642	D	0.413	neutral	N	0.48472688	None	None	N
R/V	0.2816	likely_benign	0.228	benign	-0.277	Destabilizing	0.704	D	0.459	neutral	None	None	None	None	N
R/W	0.1749	likely_benign	0.1376	benign	-0.382	Destabilizing	0.995	D	0.362	neutral	None	None	None	None	N
R/Y	0.3489	ambiguous	0.2714	benign	-0.089	Destabilizing	0.543	D	0.435	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.