TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23789	71590;71591;71592	chr2:178574767;178574766;178574765	chr2:179439494;179439493;179439492
N2AB	22148	66667;66668;66669	chr2:178574767;178574766;178574765	chr2:179439494;179439493;179439492
N2A	21221	63886;63887;63888	chr2:178574767;178574766;178574765	chr2:179439494;179439493;179439492
N2B	14724	44395;44396;44397	chr2:178574767;178574766;178574765	chr2:179439494;179439493;179439492
Novex-1	14849	44770;44771;44772	chr2:178574767;178574766;178574765	chr2:179439494;179439493;179439492
Novex-2	14916	44971;44972;44973	chr2:178574767;178574766;178574765	chr2:179439494;179439493;179439492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-60
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4226
• 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	None	None	0.002	N	0.127	0.103	0.148003135375	gnomAD-4.0.0	6.84911E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65876E-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
T/A	0.0902	likely_benign	0.067	benign	-0.606	Destabilizing	0.002	N	0.127	neutral	N	0.49778103	None	None	N
T/C	0.3763	ambiguous	0.3093	benign	-0.436	Destabilizing	0.92	D	0.551	neutral	None	None	None	None	N
T/D	0.7197	likely_pathogenic	0.6474	pathogenic	0.225	Stabilizing	0.617	D	0.53	neutral	None	None	None	None	N
T/E	0.6222	likely_pathogenic	0.5709	pathogenic	0.226	Stabilizing	0.617	D	0.485	neutral	None	None	None	None	N
T/F	0.3842	ambiguous	0.2838	benign	-0.7	Destabilizing	0.85	D	0.574	neutral	None	None	None	None	N
T/G	0.1885	likely_benign	0.1523	benign	-0.85	Destabilizing	0.447	N	0.488	neutral	None	None	None	None	N
T/H	0.4182	ambiguous	0.3588	ambiguous	-1.016	Destabilizing	0.992	D	0.548	neutral	None	None	None	None	N
T/I	0.2349	likely_benign	0.1618	benign	-0.057	Destabilizing	0.004	N	0.301	neutral	N	0.473462834	None	None	N
T/K	0.4496	ambiguous	0.4186	ambiguous	-0.555	Destabilizing	0.617	D	0.521	neutral	None	None	None	None	N
T/L	0.1201	likely_benign	0.0914	benign	-0.057	Destabilizing	0.103	N	0.407	neutral	None	None	None	None	N
T/M	0.1104	likely_benign	0.0857	benign	-0.035	Destabilizing	0.85	D	0.559	neutral	None	None	None	None	N
T/N	0.1647	likely_benign	0.1286	benign	-0.491	Destabilizing	0.549	D	0.469	neutral	N	0.50786195	None	None	N
T/P	0.1236	likely_benign	0.0991	benign	-0.208	Destabilizing	0.896	D	0.576	neutral	N	0.510902255	None	None	N
T/Q	0.3444	ambiguous	0.3094	benign	-0.58	Destabilizing	0.92	D	0.58	neutral	None	None	None	None	N
T/R	0.4385	ambiguous	0.3908	ambiguous	-0.355	Destabilizing	0.85	D	0.591	neutral	None	None	None	None	N
T/S	0.1096	likely_benign	0.0844	benign	-0.786	Destabilizing	0.016	N	0.19	neutral	N	0.48132871	None	None	N
T/V	0.1473	likely_benign	0.1097	benign	-0.208	Destabilizing	0.021	N	0.149	neutral	None	None	None	None	N
T/W	0.7567	likely_pathogenic	0.6625	pathogenic	-0.683	Destabilizing	0.992	D	0.571	neutral	None	None	None	None	N
T/Y	0.4521	ambiguous	0.3522	ambiguous	-0.428	Destabilizing	0.92	D	0.566	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.