TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2854	8785;8786;8787	chr2:178770141;178770140;178770139	chr2:179634868;179634867;179634866
N2AB	2854	8785;8786;8787	chr2:178770141;178770140;178770139	chr2:179634868;179634867;179634866
N2A	2854	8785;8786;8787	chr2:178770141;178770140;178770139	chr2:179634868;179634867;179634866
N2B	2808	8647;8648;8649	chr2:178770141;178770140;178770139	chr2:179634868;179634867;179634866
Novex-1	2808	8647;8648;8649	chr2:178770141;178770140;178770139	chr2:179634868;179634867;179634866
Novex-2	2808	8647;8648;8649	chr2:178770141;178770140;178770139	chr2:179634868;179634867;179634866
Novex-3	2854	8785;8786;8787	chr2:178770141;178770140;178770139	chr2:179634868;179634867;179634866

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-18
• Domain position: 60
• Structural Position: 141
• Q(SASA): 0.2758
• 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	None	None	0.028	N	0.164	0.271	0.238096912614	gnomAD-4.0.0	6.84063E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65574E-05
Q/R	rs750346528	None	0.801	N	0.413	0.317	0.231873229951	gnomAD-4.0.0	1.59047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02133E-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
Q/A	0.3253	likely_benign	0.4295	ambiguous	-0.441	Destabilizing	0.842	D	0.344	neutral	None	None	None	None	N
Q/C	0.7022	likely_pathogenic	0.8054	pathogenic	0.052	Stabilizing	0.998	D	0.517	neutral	None	None	None	None	N
Q/D	0.4943	ambiguous	0.6427	pathogenic	-1.014	Destabilizing	0.842	D	0.361	neutral	None	None	None	None	N
Q/E	0.1129	likely_benign	0.1295	benign	-0.918	Destabilizing	0.625	D	0.359	neutral	N	0.502341142	None	None	N
Q/F	0.7722	likely_pathogenic	0.8625	pathogenic	-0.254	Destabilizing	0.949	D	0.516	neutral	None	None	None	None	N
Q/G	0.3581	ambiguous	0.456	ambiguous	-0.799	Destabilizing	0.842	D	0.437	neutral	None	None	None	None	N
Q/H	0.2271	likely_benign	0.3356	benign	-0.878	Destabilizing	0.028	N	0.164	neutral	N	0.479643097	None	None	N
Q/I	0.5408	ambiguous	0.6595	pathogenic	0.468	Stabilizing	0.904	D	0.464	neutral	None	None	None	None	N
Q/K	0.1324	likely_benign	0.1591	benign	-0.297	Destabilizing	0.801	D	0.382	neutral	N	0.494406951	None	None	N
Q/L	0.1976	likely_benign	0.2625	benign	0.468	Stabilizing	0.012	N	0.253	neutral	N	0.504073255	None	None	N
Q/M	0.4662	ambiguous	0.5781	pathogenic	0.991	Stabilizing	0.949	D	0.408	neutral	None	None	None	None	N
Q/N	0.3395	likely_benign	0.4679	ambiguous	-0.885	Destabilizing	0.842	D	0.353	neutral	None	None	None	None	N
Q/P	0.3827	ambiguous	0.529	ambiguous	0.197	Stabilizing	0.989	D	0.432	neutral	N	0.510244506	None	None	N
Q/R	0.1396	likely_benign	0.1604	benign	-0.29	Destabilizing	0.801	D	0.413	neutral	N	0.494583541	None	None	N
Q/S	0.3309	likely_benign	0.4211	ambiguous	-0.904	Destabilizing	0.842	D	0.319	neutral	None	None	None	None	N
Q/T	0.2911	likely_benign	0.3802	ambiguous	-0.619	Destabilizing	0.915	D	0.383	neutral	None	None	None	None	N
Q/V	0.3735	ambiguous	0.4758	ambiguous	0.197	Stabilizing	0.728	D	0.416	neutral	None	None	None	None	N
Q/W	0.6328	likely_pathogenic	0.7274	pathogenic	-0.21	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
Q/Y	0.5374	ambiguous	0.6837	pathogenic	0.08	Stabilizing	0.949	D	0.414	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.