TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20802	62629;62630;62631	chr2:178589321;178589320;178589319	chr2:179454048;179454047;179454046
N2AB	19161	57706;57707;57708	chr2:178589321;178589320;178589319	chr2:179454048;179454047;179454046
N2A	18234	54925;54926;54927	chr2:178589321;178589320;178589319	chr2:179454048;179454047;179454046
N2B	11737	35434;35435;35436	chr2:178589321;178589320;178589319	chr2:179454048;179454047;179454046
Novex-1	11862	35809;35810;35811	chr2:178589321;178589320;178589319	chr2:179454048;179454047;179454046
Novex-2	11929	36010;36011;36012	chr2:178589321;178589320;178589319	chr2:179454048;179454047;179454046
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-122
• Domain position: 34
• Structural Position: 47
• Q(SASA): 0.3308
• 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
A/V	rs1285688683	None	None	N	0.249	0.085	0.124217242631	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
A/V	rs1285688683	None	None	N	0.249	0.085	0.124217242631	gnomAD-4.0.0	6.57748E-06	None	None	None	None	N	None	0	6.55652E-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
A/C	0.2329	likely_benign	0.2441	benign	-0.778	Destabilizing	0.356	N	0.499	neutral	None	None	None	None	N
A/D	0.3185	likely_benign	0.2905	benign	-0.654	Destabilizing	0.038	N	0.536	neutral	None	None	None	None	N
A/E	0.2258	likely_benign	0.2008	benign	-0.74	Destabilizing	0.012	N	0.443	neutral	N	0.422022195	None	None	N
A/F	0.1666	likely_benign	0.1467	benign	-0.8	Destabilizing	0.12	N	0.584	neutral	None	None	None	None	N
A/G	0.1432	likely_benign	0.1437	benign	-0.63	Destabilizing	0.012	N	0.379	neutral	N	0.497618819	None	None	N
A/H	0.2617	likely_benign	0.2275	benign	-0.583	Destabilizing	0.356	N	0.545	neutral	None	None	None	None	N
A/I	0.0924	likely_benign	0.0798	benign	-0.262	Destabilizing	0.006	N	0.428	neutral	None	None	None	None	N
A/K	0.3008	likely_benign	0.2336	benign	-0.839	Destabilizing	None	N	0.255	neutral	None	None	None	None	N
A/L	0.08	likely_benign	0.0707	benign	-0.262	Destabilizing	None	N	0.237	neutral	None	None	None	None	N
A/M	0.1041	likely_benign	0.099	benign	-0.423	Destabilizing	0.12	N	0.515	neutral	None	None	None	None	N
A/N	0.1401	likely_benign	0.1394	benign	-0.621	Destabilizing	0.038	N	0.533	neutral	None	None	None	None	N
A/P	0.8907	likely_pathogenic	0.8748	pathogenic	-0.297	Destabilizing	0.055	N	0.519	neutral	D	0.527595009	None	None	N
A/Q	0.1946	likely_benign	0.168	benign	-0.814	Destabilizing	0.072	N	0.56	neutral	None	None	None	None	N
A/R	0.2962	likely_benign	0.2259	benign	-0.407	Destabilizing	0.038	N	0.485	neutral	None	None	None	None	N
A/S	0.0693	likely_benign	0.0718	benign	-0.863	Destabilizing	None	N	0.255	neutral	N	0.380519502	None	None	N
A/T	0.0551	likely_benign	0.0549	benign	-0.854	Destabilizing	None	N	0.193	neutral	N	0.334635284	None	None	N
A/V	0.0668	likely_benign	0.0601	benign	-0.297	Destabilizing	None	N	0.249	neutral	N	0.415483012	None	None	N
A/W	0.5319	ambiguous	0.4594	ambiguous	-1.033	Destabilizing	0.864	D	0.588	neutral	None	None	None	None	N
A/Y	0.2781	likely_benign	0.2521	benign	-0.648	Destabilizing	0.356	N	0.567	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.