TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7927	24004;24005;24006	chr2:178719713;178719712;178719711	chr2:179584440;179584439;179584438
N2AB	7610	23053;23054;23055	chr2:178719713;178719712;178719711	chr2:179584440;179584439;179584438
N2A	6683	20272;20273;20274	chr2:178719713;178719712;178719711	chr2:179584440;179584439;179584438
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-64
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.77
• 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	0.189	0.106	0.101711395817	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	0.2165	likely_benign	0.26	benign	0.078	Stabilizing	0.002	N	0.209	neutral	None	None	None	None	N
R/C	0.1586	likely_benign	0.1883	benign	-0.143	Destabilizing	0.958	D	0.271	neutral	None	None	None	None	N
R/D	0.4054	ambiguous	0.491	ambiguous	-0.129	Destabilizing	0.22	N	0.426	neutral	None	None	None	None	N
R/E	0.1733	likely_benign	0.2097	benign	-0.07	Destabilizing	0.055	N	0.31	neutral	None	None	None	None	N
R/F	0.3148	likely_benign	0.3855	ambiguous	-0.177	Destabilizing	0.667	D	0.343	neutral	None	None	None	None	N
R/G	0.1687	likely_benign	0.2067	benign	-0.1	Destabilizing	0.081	N	0.376	neutral	N	0.515223145	None	None	N
R/H	0.0893	likely_benign	0.0977	benign	-0.603	Destabilizing	0.667	D	0.311	neutral	None	None	None	None	N
R/I	0.1193	likely_benign	0.1398	benign	0.505	Stabilizing	0.003	N	0.27	neutral	N	0.506334303	None	None	N
R/K	0.0685	likely_benign	0.0713	benign	-0.031	Destabilizing	None	N	0.189	neutral	N	0.414576148	None	None	N
R/L	0.1439	likely_benign	0.1695	benign	0.505	Stabilizing	0.055	N	0.341	neutral	None	None	None	None	N
R/M	0.1249	likely_benign	0.1421	benign	0.03	Stabilizing	0.667	D	0.324	neutral	None	None	None	None	N
R/N	0.285	likely_benign	0.3388	benign	0.106	Stabilizing	0.22	N	0.317	neutral	None	None	None	None	N
R/P	0.8106	likely_pathogenic	0.8578	pathogenic	0.383	Stabilizing	0.364	N	0.397	neutral	None	None	None	None	N
R/Q	0.0786	likely_benign	0.0832	benign	0.049	Stabilizing	0.124	N	0.323	neutral	None	None	None	None	N
R/S	0.2562	likely_benign	0.3119	benign	-0.16	Destabilizing	0.042	N	0.391	neutral	N	0.493978294	None	None	N
R/T	0.1244	likely_benign	0.15	benign	0.025	Stabilizing	0.081	N	0.379	neutral	N	0.5126442	None	None	N
R/V	0.1661	likely_benign	0.1924	benign	0.383	Stabilizing	0.002	N	0.251	neutral	None	None	None	None	N
R/W	0.1354	likely_benign	0.155	benign	-0.3	Destabilizing	0.958	D	0.274	neutral	None	None	None	None	N
R/Y	0.2503	likely_benign	0.308	benign	0.119	Stabilizing	0.859	D	0.34	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.