TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5602	17029;17030;17031	chr2:178732165;178732164;178732163	chr2:179596892;179596891;179596890
N2AB	5285	16078;16079;16080	chr2:178732165;178732164;178732163	chr2:179596892;179596891;179596890
N2A	4358	13297;13298;13299	chr2:178732165;178732164;178732163	chr2:179596892;179596891;179596890
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-39
• Domain position: 60
• Structural Position: 139
• Q(SASA): 0.6285
• 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/G	None	None	0.012	N	0.44	0.31	0.441221003447	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	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	0.1253	likely_benign	0.1511	benign	-0.956	Destabilizing	0.016	N	0.352	neutral	None	None	None	None	N
R/C	0.1068	likely_benign	0.1233	benign	-0.893	Destabilizing	0.676	D	0.437	neutral	None	None	None	None	N
R/D	0.2629	likely_benign	0.3161	benign	-0.011	Destabilizing	0.016	N	0.443	neutral	None	None	None	None	N
R/E	0.1317	likely_benign	0.1487	benign	0.1	Stabilizing	None	N	0.205	neutral	None	None	None	None	N
R/F	0.1859	likely_benign	0.2039	benign	-0.843	Destabilizing	0.356	N	0.454	neutral	None	None	None	None	N
R/G	0.1153	likely_benign	0.1404	benign	-1.248	Destabilizing	0.012	N	0.44	neutral	N	0.496736828	None	None	N
R/H	0.0643	likely_benign	0.0646	benign	-1.404	Destabilizing	None	N	0.21	neutral	None	None	None	None	N
R/I	0.0858	likely_benign	0.0893	benign	-0.174	Destabilizing	0.093	N	0.503	neutral	N	0.460620656	None	None	N
R/K	0.0687	likely_benign	0.0747	benign	-0.9	Destabilizing	0.012	N	0.377	neutral	N	0.470568291	None	None	N
R/L	0.0851	likely_benign	0.093	benign	-0.174	Destabilizing	0.038	N	0.496	neutral	None	None	None	None	N
R/M	0.083	likely_benign	0.0887	benign	-0.429	Destabilizing	0.356	N	0.465	neutral	None	None	None	None	N
R/N	0.1701	likely_benign	0.1985	benign	-0.278	Destabilizing	0.016	N	0.402	neutral	None	None	None	None	N
R/P	0.7131	likely_pathogenic	0.7828	pathogenic	-0.415	Destabilizing	0.072	N	0.507	neutral	None	None	None	None	N
R/Q	0.0649	likely_benign	0.0682	benign	-0.523	Destabilizing	0.072	N	0.413	neutral	None	None	None	None	N
R/S	0.1228	likely_benign	0.1466	benign	-1.145	Destabilizing	None	N	0.263	neutral	N	0.482054721	None	None	N
R/T	0.0637	likely_benign	0.068	benign	-0.859	Destabilizing	None	N	0.269	neutral	N	0.416443017	None	None	N
R/V	0.1143	likely_benign	0.1284	benign	-0.415	Destabilizing	0.038	N	0.495	neutral	None	None	None	None	N
R/W	0.0906	likely_benign	0.0978	benign	-0.447	Destabilizing	0.864	D	0.447	neutral	None	None	None	None	N
R/Y	0.1402	likely_benign	0.1504	benign	-0.167	Destabilizing	0.214	N	0.511	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.