TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8871	26836;26837;26838	chr2:178714047;178714046;178714045	chr2:179578774;179578773;179578772
N2AB	8554	25885;25886;25887	chr2:178714047;178714046;178714045	chr2:179578774;179578773;179578772
N2A	7627	23104;23105;23106	chr2:178714047;178714046;178714045	chr2:179578774;179578773;179578772
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-74
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.5774
• 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
T/A	rs2077092454	None	None	N	0.117	0.1	0.126345400529	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/A	rs2077092454	None	None	N	0.117	0.1	0.126345400529	gnomAD-4.0.0	6.57272E-06	None	None	None	None	N	None	0	6.54965E-05	None	0	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
T/A	0.0688	likely_benign	0.0718	benign	-0.337	Destabilizing	None	N	0.117	neutral	N	0.491999569	None	None	N
T/C	0.3034	likely_benign	0.2981	benign	-0.386	Destabilizing	0.356	N	0.359	neutral	None	None	None	None	N
T/D	0.2672	likely_benign	0.2857	benign	0.3	Stabilizing	0.072	N	0.333	neutral	None	None	None	None	N
T/E	0.2055	likely_benign	0.2193	benign	0.252	Stabilizing	0.016	N	0.325	neutral	None	None	None	None	N
T/F	0.1283	likely_benign	0.1399	benign	-0.858	Destabilizing	0.214	N	0.439	neutral	None	None	None	None	N
T/G	0.1708	likely_benign	0.1731	benign	-0.476	Destabilizing	0.016	N	0.294	neutral	None	None	None	None	N
T/H	0.1393	likely_benign	0.1427	benign	-0.645	Destabilizing	0.628	D	0.382	neutral	None	None	None	None	N
T/I	0.0926	likely_benign	0.0967	benign	-0.091	Destabilizing	0.012	N	0.328	neutral	N	0.512780272	None	None	N
T/K	0.1045	likely_benign	0.1024	benign	-0.251	Destabilizing	None	N	0.185	neutral	N	0.461425945	None	None	N
T/L	0.0665	likely_benign	0.0696	benign	-0.091	Destabilizing	0.002	N	0.266	neutral	None	None	None	None	N
T/M	0.076	likely_benign	0.0828	benign	-0.169	Destabilizing	0.002	N	0.223	neutral	None	None	None	None	N
T/N	0.094	likely_benign	0.0989	benign	-0.179	Destabilizing	0.072	N	0.194	neutral	None	None	None	None	N
T/P	0.0849	likely_benign	0.0977	benign	-0.144	Destabilizing	0.055	N	0.355	neutral	N	0.443747049	None	None	N
T/Q	0.1309	likely_benign	0.1338	benign	-0.301	Destabilizing	0.072	N	0.406	neutral	None	None	None	None	N
T/R	0.0901	likely_benign	0.0877	benign	-0.016	Destabilizing	0.029	N	0.376	neutral	N	0.456097483	None	None	N
T/S	0.0834	likely_benign	0.0853	benign	-0.39	Destabilizing	None	N	0.123	neutral	N	0.424947857	None	None	N
T/V	0.0919	likely_benign	0.0928	benign	-0.144	Destabilizing	None	N	0.151	neutral	None	None	None	None	N
T/W	0.3799	ambiguous	0.3995	ambiguous	-0.914	Destabilizing	0.864	D	0.384	neutral	None	None	None	None	N
T/Y	0.1639	likely_benign	0.1717	benign	-0.589	Destabilizing	0.356	N	0.422	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.