TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7235	21928;21929;21930	chr2:178723304;178723303;178723302	chr2:179588031;179588030;179588029
N2AB	6918	20977;20978;20979	chr2:178723304;178723303;178723302	chr2:179588031;179588030;179588029
N2A	5991	18196;18197;18198	chr2:178723304;178723303;178723302	chr2:179588031;179588030;179588029
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-57
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.845
• Predicted PPI site: I

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	None	N	0.18	0.125	0.453867917445	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/S	rs772506057	-0.055	0.012	N	0.311	0.1	0.0762999501168	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	1.00281E-04	0	None	0	None	0	0	0
R/S	rs772506057	-0.055	0.012	N	0.311	0.1	0.0762999501168	gnomAD-4.0.0	1.59434E-06	None	None	None	None	I	None	0	0	None	4.77783E-05	0	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	0.2834	likely_benign	0.283	benign	-0.833	Destabilizing	0.007	N	0.275	neutral	None	None	None	None	I
R/C	0.2409	likely_benign	0.2432	benign	-0.777	Destabilizing	0.864	D	0.259	neutral	None	None	None	None	I
R/D	0.5543	ambiguous	0.5706	pathogenic	0.171	Stabilizing	0.031	N	0.375	neutral	None	None	None	None	I
R/E	0.2503	likely_benign	0.2558	benign	0.298	Stabilizing	0.007	N	0.227	neutral	None	None	None	None	I
R/F	0.5179	ambiguous	0.5245	ambiguous	-0.684	Destabilizing	0.628	D	0.309	neutral	None	None	None	None	I
R/G	0.1567	likely_benign	0.1619	benign	-1.127	Destabilizing	None	N	0.18	neutral	N	0.496194667	None	None	I
R/H	0.1269	likely_benign	0.1341	benign	-1.36	Destabilizing	0.356	N	0.355	neutral	None	None	None	None	I
R/I	0.2338	likely_benign	0.2487	benign	-0.046	Destabilizing	0.295	N	0.349	neutral	N	0.521204968	None	None	I
R/K	0.0633	likely_benign	0.0609	benign	-0.62	Destabilizing	None	N	0.148	neutral	N	0.394104875	None	None	I
R/L	0.2173	likely_benign	0.2178	benign	-0.046	Destabilizing	0.031	N	0.345	neutral	None	None	None	None	I
R/M	0.1813	likely_benign	0.189	benign	-0.431	Destabilizing	0.628	D	0.33	neutral	None	None	None	None	I
R/N	0.3882	ambiguous	0.3953	ambiguous	-0.178	Destabilizing	0.031	N	0.297	neutral	None	None	None	None	I
R/P	0.2698	likely_benign	0.2331	benign	-0.288	Destabilizing	0.136	N	0.432	neutral	None	None	None	None	I
R/Q	0.0988	likely_benign	0.1014	benign	-0.334	Destabilizing	0.003	N	0.213	neutral	None	None	None	None	I
R/S	0.3243	likely_benign	0.336	benign	-1.009	Destabilizing	0.012	N	0.311	neutral	N	0.497386746	None	None	I
R/T	0.1685	likely_benign	0.1816	benign	-0.697	Destabilizing	0.024	N	0.348	neutral	N	0.476915473	None	None	I
R/V	0.2949	likely_benign	0.3057	benign	-0.288	Destabilizing	0.072	N	0.435	neutral	None	None	None	None	I
R/W	0.2105	likely_benign	0.2222	benign	-0.352	Destabilizing	0.864	D	0.261	neutral	None	None	None	None	I
R/Y	0.3876	ambiguous	0.388	ambiguous	-0.067	Destabilizing	0.356	N	0.337	neutral	None	None	None	None	I

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.