TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27624	83095;83096;83097	chr2:178563262;178563261;178563260	chr2:179427989;179427988;179427987
N2AB	25983	78172;78173;78174	chr2:178563262;178563261;178563260	chr2:179427989;179427988;179427987
N2A	25056	75391;75392;75393	chr2:178563262;178563261;178563260	chr2:179427989;179427988;179427987
N2B	18559	55900;55901;55902	chr2:178563262;178563261;178563260	chr2:179427989;179427988;179427987
Novex-1	18684	56275;56276;56277	chr2:178563262;178563261;178563260	chr2:179427989;179427988;179427987
Novex-2	18751	56476;56477;56478	chr2:178563262;178563261;178563260	chr2:179427989;179427988;179427987
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-89
• Domain position: 55
• Structural Position: 74
• Q(SASA): 0.813
• 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
T/I	rs1001331770	None	0.497	N	0.423	0.315	0.353974658523	gnomAD-4.0.0	1.59145E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
T/A	0.0603	likely_benign	0.0639	benign	-0.208	Destabilizing	0.055	N	0.447	neutral	N	0.447578709	None	None	I
T/C	0.334	likely_benign	0.3579	ambiguous	-0.24	Destabilizing	0.909	D	0.473	neutral	None	None	None	None	I
T/D	0.2592	likely_benign	0.2977	benign	0.122	Stabilizing	0.157	N	0.44	neutral	None	None	None	None	I
T/E	0.2167	likely_benign	0.2418	benign	0.028	Stabilizing	0.157	N	0.435	neutral	None	None	None	None	I
T/F	0.2082	likely_benign	0.2216	benign	-0.852	Destabilizing	0.726	D	0.54	neutral	None	None	None	None	I
T/G	0.1354	likely_benign	0.1588	benign	-0.277	Destabilizing	0.001	N	0.297	neutral	None	None	None	None	I
T/H	0.2169	likely_benign	0.2362	benign	-0.515	Destabilizing	0.909	D	0.544	neutral	None	None	None	None	I
T/I	0.192	likely_benign	0.1978	benign	-0.15	Destabilizing	0.497	N	0.423	neutral	N	0.476594894	None	None	I
T/K	0.1785	likely_benign	0.1889	benign	-0.22	Destabilizing	0.331	N	0.423	neutral	N	0.489425331	None	None	I
T/L	0.0937	likely_benign	0.094	benign	-0.15	Destabilizing	0.272	N	0.463	neutral	None	None	None	None	I
T/M	0.0906	likely_benign	0.0896	benign	-0.052	Destabilizing	0.968	D	0.442	neutral	None	None	None	None	I
T/N	0.1054	likely_benign	0.1178	benign	0.011	Stabilizing	0.157	N	0.4	neutral	None	None	None	None	I
T/P	0.1274	likely_benign	0.1274	benign	-0.145	Destabilizing	0.497	N	0.427	neutral	N	0.511320756	None	None	I
T/Q	0.1839	likely_benign	0.1948	benign	-0.222	Destabilizing	0.567	D	0.415	neutral	None	None	None	None	I
T/R	0.1607	likely_benign	0.165	benign	0.048	Stabilizing	0.497	N	0.421	neutral	N	0.482016569	None	None	I
T/S	0.0783	likely_benign	0.0875	benign	-0.169	Destabilizing	0.001	N	0.17	neutral	N	0.474687952	None	None	I
T/V	0.125	likely_benign	0.1279	benign	-0.145	Destabilizing	0.272	N	0.424	neutral	None	None	None	None	I
T/W	0.4823	ambiguous	0.5054	ambiguous	-0.91	Destabilizing	0.968	D	0.639	neutral	None	None	None	None	I
T/Y	0.2475	likely_benign	0.2686	benign	-0.594	Destabilizing	0.726	D	0.542	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.