TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26850	80773;80774;80775	chr2:178565584;178565583;178565582	chr2:179430311;179430310;179430309
N2AB	25209	75850;75851;75852	chr2:178565584;178565583;178565582	chr2:179430311;179430310;179430309
N2A	24282	73069;73070;73071	chr2:178565584;178565583;178565582	chr2:179430311;179430310;179430309
N2B	17785	53578;53579;53580	chr2:178565584;178565583;178565582	chr2:179430311;179430310;179430309
Novex-1	17910	53953;53954;53955	chr2:178565584;178565583;178565582	chr2:179430311;179430310;179430309
Novex-2	17977	54154;54155;54156	chr2:178565584;178565583;178565582	chr2:179430311;179430310;179430309
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-83
• Domain position: 71
• Structural Position: 105
• Q(SASA): 0.211
• 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
Q/H	rs1705482872	None	None	N	0.293	0.067	0.110078149338	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/H	rs1705482872	None	None	N	0.293	0.067	0.110078149338	gnomAD-4.0.0	6.57436E-06	None	None	None	None	N	None	2.41324E-05	0	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
Q/A	0.1941	likely_benign	0.1955	benign	-0.962	Destabilizing	0.004	N	0.37	neutral	None	None	None	None	N
Q/C	0.413	ambiguous	0.4475	ambiguous	-0.432	Destabilizing	0.497	N	0.577	neutral	None	None	None	None	N
Q/D	0.3644	ambiguous	0.35	ambiguous	-2.098	Highly Destabilizing	0.018	N	0.456	neutral	None	None	None	None	N
Q/E	0.0988	likely_benign	0.0872	benign	-1.765	Destabilizing	0.003	N	0.358	neutral	N	0.41902667	None	None	N
Q/F	0.4195	ambiguous	0.456	ambiguous	-0.363	Destabilizing	0.044	N	0.558	neutral	None	None	None	None	N
Q/G	0.2952	likely_benign	0.2905	benign	-1.423	Destabilizing	0.009	N	0.459	neutral	None	None	None	None	N
Q/H	0.1302	likely_benign	0.1436	benign	-0.89	Destabilizing	None	N	0.293	neutral	N	0.46695669	None	None	N
Q/I	0.2159	likely_benign	0.2223	benign	0.325	Stabilizing	0.009	N	0.499	neutral	None	None	None	None	N
Q/K	0.1491	likely_benign	0.1338	benign	-0.354	Destabilizing	0.003	N	0.377	neutral	N	0.438095221	None	None	N
Q/L	0.0832	likely_benign	0.0852	benign	0.325	Stabilizing	None	N	0.385	neutral	N	0.419280174	None	None	N
Q/M	0.2265	likely_benign	0.2406	benign	0.298	Stabilizing	0.002	N	0.321	neutral	None	None	None	None	N
Q/N	0.1947	likely_benign	0.2162	benign	-1.292	Destabilizing	0.009	N	0.459	neutral	None	None	None	None	N
Q/P	0.6474	likely_pathogenic	0.6297	pathogenic	-0.082	Destabilizing	0.065	N	0.549	neutral	N	0.479143919	None	None	N
Q/R	0.1341	likely_benign	0.122	benign	-0.641	Destabilizing	None	N	0.271	neutral	N	0.399115545	None	None	N
Q/S	0.1574	likely_benign	0.186	benign	-1.558	Destabilizing	None	N	0.252	neutral	None	None	None	None	N
Q/T	0.1399	likely_benign	0.1431	benign	-1.047	Destabilizing	0.009	N	0.408	neutral	None	None	None	None	N
Q/V	0.1533	likely_benign	0.155	benign	-0.082	Destabilizing	0.004	N	0.441	neutral	None	None	None	None	N
Q/W	0.4121	ambiguous	0.4101	ambiguous	-0.529	Destabilizing	0.788	D	0.576	neutral	None	None	None	None	N
Q/Y	0.2491	likely_benign	0.2705	benign	-0.07	Destabilizing	0.022	N	0.545	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.