TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3251	9976;9977;9978	chr2:178764764;178764763;178764762	chr2:179629491;179629490;179629489
N2AB	3251	9976;9977;9978	chr2:178764764;178764763;178764762	chr2:179629491;179629490;179629489
N2A	3251	9976;9977;9978	chr2:178764764;178764763;178764762	chr2:179629491;179629490;179629489
N2B	3205	9838;9839;9840	chr2:178764764;178764763;178764762	chr2:179629491;179629490;179629489
Novex-1	3205	9838;9839;9840	chr2:178764764;178764763;178764762	chr2:179629491;179629490;179629489
Novex-2	3205	9838;9839;9840	chr2:178764764;178764763;178764762	chr2:179629491;179629490;179629489
Novex-3	3251	9976;9977;9978	chr2:178764764;178764763;178764762	chr2:179629491;179629490;179629489

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-23
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.7326
• 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/L	None	None	0.351	N	0.446	0.288	0.488897681448	gnomAD-4.0.0	1.36833E-06	None	None	None	None	N	None	0	0	None	0	5.03956E-05	None	0	0	0	0	0
Q/R	None	None	0.183	N	0.339	0.244	0.163833314356	gnomAD-4.0.0	6.84167E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99331E-07	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	0.1804	likely_benign	0.2319	benign	-0.204	Destabilizing	0.129	N	0.395	neutral	None	None	None	None	N
Q/C	0.6942	likely_pathogenic	0.8664	pathogenic	0.108	Stabilizing	0.983	D	0.446	neutral	None	None	None	None	N
Q/D	0.3968	ambiguous	0.6141	pathogenic	0.042	Stabilizing	0.061	N	0.277	neutral	None	None	None	None	N
Q/E	0.0685	likely_benign	0.0773	benign	0.014	Stabilizing	None	N	0.19	neutral	N	0.383616437	None	None	N
Q/F	0.678	likely_pathogenic	0.8231	pathogenic	-0.395	Destabilizing	0.94	D	0.451	neutral	None	None	None	None	N
Q/G	0.3348	likely_benign	0.4874	ambiguous	-0.389	Destabilizing	0.228	N	0.457	neutral	None	None	None	None	N
Q/H	0.2632	likely_benign	0.4237	ambiguous	-0.253	Destabilizing	0.794	D	0.343	neutral	N	0.479920261	None	None	N
Q/I	0.3478	ambiguous	0.4527	ambiguous	0.193	Stabilizing	0.836	D	0.457	neutral	None	None	None	None	N
Q/K	0.1128	likely_benign	0.1559	benign	0.055	Stabilizing	0.047	N	0.285	neutral	N	0.444503174	None	None	N
Q/L	0.1255	likely_benign	0.1701	benign	0.193	Stabilizing	0.351	N	0.446	neutral	N	0.414070036	None	None	N
Q/M	0.3448	ambiguous	0.4353	ambiguous	0.381	Stabilizing	0.94	D	0.366	neutral	None	None	None	None	N
Q/N	0.3416	ambiguous	0.4998	ambiguous	-0.297	Destabilizing	0.418	N	0.307	neutral	None	None	None	None	N
Q/P	0.1156	likely_benign	0.1588	benign	0.089	Stabilizing	0.523	D	0.406	neutral	N	0.437925905	None	None	N
Q/R	0.1233	likely_benign	0.1856	benign	0.212	Stabilizing	0.183	N	0.339	neutral	N	0.455769223	None	None	N
Q/S	0.2428	likely_benign	0.3577	ambiguous	-0.289	Destabilizing	0.129	N	0.341	neutral	None	None	None	None	N
Q/T	0.1878	likely_benign	0.2668	benign	-0.162	Destabilizing	0.418	N	0.404	neutral	None	None	None	None	N
Q/V	0.2298	likely_benign	0.288	benign	0.089	Stabilizing	0.418	N	0.474	neutral	None	None	None	None	N
Q/W	0.6299	likely_pathogenic	0.824	pathogenic	-0.372	Destabilizing	0.983	D	0.46	neutral	None	None	None	None	N
Q/Y	0.5159	ambiguous	0.7028	pathogenic	-0.117	Destabilizing	0.94	D	0.418	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.