TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5404	16435;16436;16437	chr2:178732966;178732965;178732964	chr2:179597693;179597692;179597691
N2AB	5087	15484;15485;15486	chr2:178732966;178732965;178732964	chr2:179597693;179597692;179597691
N2A	4160	12703;12704;12705	chr2:178732966;178732965;178732964	chr2:179597693;179597692;179597691
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: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-37
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.6471
• 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/S	rs758704167	-0.528	0.012	N	0.253	0.12	0.299770980665	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
R/S	rs758704167	-0.528	0.012	N	0.253	0.12	0.299770980665	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
R/S	rs758704167	-0.528	0.012	N	0.253	0.12	0.299770980665	gnomAD-4.0.0	1.30154E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69528E-05	0	1.60164E-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	0.2302	likely_benign	0.2188	benign	-0.604	Destabilizing	0.007	N	0.207	neutral	None	None	None	None	I
R/C	0.1615	likely_benign	0.16	benign	-0.586	Destabilizing	0.864	D	0.263	neutral	None	None	None	None	I
R/D	0.3793	ambiguous	0.3658	ambiguous	0.009	Stabilizing	0.031	N	0.338	neutral	None	None	None	None	I
R/E	0.2129	likely_benign	0.1982	benign	0.1	Stabilizing	0.007	N	0.183	neutral	None	None	None	None	I
R/F	0.411	ambiguous	0.4152	ambiguous	-0.65	Destabilizing	0.214	N	0.33	neutral	None	None	None	None	I
R/G	0.154	likely_benign	0.1508	benign	-0.863	Destabilizing	0.024	N	0.307	neutral	D	0.534849056	None	None	I
R/H	0.0768	likely_benign	0.0765	benign	-1.17	Destabilizing	0.214	N	0.309	neutral	None	None	None	None	I
R/I	0.1957	likely_benign	0.1925	benign	0.069	Stabilizing	0.038	N	0.408	neutral	None	None	None	None	I
R/K	0.09	likely_benign	0.0841	benign	-0.596	Destabilizing	None	N	0.094	neutral	N	0.488169829	None	None	I
R/L	0.1649	likely_benign	0.1625	benign	0.069	Stabilizing	None	N	0.157	neutral	None	None	None	None	I
R/M	0.2119	likely_benign	0.2017	benign	-0.208	Destabilizing	0.171	N	0.284	neutral	N	0.491025609	None	None	I
R/N	0.2723	likely_benign	0.2607	benign	-0.088	Destabilizing	0.031	N	0.251	neutral	None	None	None	None	I
R/P	0.7509	likely_pathogenic	0.7356	pathogenic	-0.135	Destabilizing	0.136	N	0.397	neutral	None	None	None	None	I
R/Q	0.0758	likely_benign	0.0747	benign	-0.306	Destabilizing	None	N	0.117	neutral	None	None	None	None	I
R/S	0.2243	likely_benign	0.2126	benign	-0.792	Destabilizing	0.012	N	0.253	neutral	N	0.499445616	None	None	I
R/T	0.1284	likely_benign	0.1224	benign	-0.54	Destabilizing	None	N	0.135	neutral	N	0.441496177	None	None	I
R/V	0.2324	likely_benign	0.2272	benign	-0.135	Destabilizing	0.016	N	0.312	neutral	None	None	None	None	I
R/W	0.1688	likely_benign	0.1701	benign	-0.409	Destabilizing	0.828	D	0.261	neutral	N	0.516473698	None	None	I
R/Y	0.2856	likely_benign	0.2833	benign	-0.074	Destabilizing	0.356	N	0.354	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.