TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24037	72334;72335;72336	chr2:178574023;178574022;178574021	chr2:179438750;179438749;179438748
N2AB	22396	67411;67412;67413	chr2:178574023;178574022;178574021	chr2:179438750;179438749;179438748
N2A	21469	64630;64631;64632	chr2:178574023;178574022;178574021	chr2:179438750;179438749;179438748
N2B	14972	45139;45140;45141	chr2:178574023;178574022;178574021	chr2:179438750;179438749;179438748
Novex-1	15097	45514;45515;45516	chr2:178574023;178574022;178574021	chr2:179438750;179438749;179438748
Novex-2	15164	45715;45716;45717	chr2:178574023;178574022;178574021	chr2:179438750;179438749;179438748
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-131
• Domain position: 9
• Structural Position: 9
• Q(SASA): 0.7383
• Predicted PPI site: I

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
D/N	rs916450369	None	0.961	N	0.449	0.188	0.167679373172	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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
D/A	0.3213	likely_benign	0.3063	benign	0.012	Stabilizing	0.835	D	0.455	neutral	N	0.454589251	None	None	I
D/C	0.8368	likely_pathogenic	0.8135	pathogenic	0.142	Stabilizing	1.0	D	0.587	neutral	None	None	None	None	I
D/E	0.1881	likely_benign	0.1833	benign	-0.238	Destabilizing	0.91	D	0.443	neutral	N	0.443988538	None	None	I
D/F	0.8421	likely_pathogenic	0.8357	pathogenic	-0.157	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	I
D/G	0.1838	likely_benign	0.1645	benign	-0.114	Destabilizing	0.031	N	0.278	neutral	N	0.498593814	None	None	I
D/H	0.474	ambiguous	0.4496	ambiguous	0.225	Stabilizing	1.0	D	0.46	neutral	N	0.461933085	None	None	I
D/I	0.7156	likely_pathogenic	0.6962	pathogenic	0.273	Stabilizing	0.996	D	0.567	neutral	None	None	None	None	I
D/K	0.5545	ambiguous	0.5248	ambiguous	0.517	Stabilizing	0.97	D	0.443	neutral	None	None	None	None	I
D/L	0.7062	likely_pathogenic	0.6814	pathogenic	0.273	Stabilizing	0.996	D	0.521	neutral	None	None	None	None	I
D/M	0.8242	likely_pathogenic	0.8145	pathogenic	0.245	Stabilizing	1.0	D	0.577	neutral	None	None	None	None	I
D/N	0.1331	likely_benign	0.1356	benign	0.391	Stabilizing	0.961	D	0.449	neutral	N	0.485221872	None	None	I
D/P	0.8657	likely_pathogenic	0.8415	pathogenic	0.206	Stabilizing	0.996	D	0.446	neutral	None	None	None	None	I
D/Q	0.4844	ambiguous	0.45	ambiguous	0.375	Stabilizing	0.996	D	0.411	neutral	None	None	None	None	I
D/R	0.6362	likely_pathogenic	0.6023	pathogenic	0.643	Stabilizing	0.996	D	0.534	neutral	None	None	None	None	I
D/S	0.2136	likely_benign	0.2098	benign	0.28	Stabilizing	0.348	N	0.195	neutral	None	None	None	None	I
D/T	0.4121	ambiguous	0.3938	ambiguous	0.373	Stabilizing	0.942	D	0.417	neutral	None	None	None	None	I
D/V	0.4668	ambiguous	0.4451	ambiguous	0.206	Stabilizing	0.994	D	0.534	neutral	N	0.513755268	None	None	I
D/W	0.956	likely_pathogenic	0.9484	pathogenic	-0.132	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
D/Y	0.4074	ambiguous	0.3787	ambiguous	0.067	Stabilizing	0.998	D	0.573	neutral	N	0.473960953	None	None	I

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.