TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20580	61963;61964;61965	chr2:178589987;178589986;178589985	chr2:179454714;179454713;179454712
N2AB	18939	57040;57041;57042	chr2:178589987;178589986;178589985	chr2:179454714;179454713;179454712
N2A	18012	54259;54260;54261	chr2:178589987;178589986;178589985	chr2:179454714;179454713;179454712
N2B	11515	34768;34769;34770	chr2:178589987;178589986;178589985	chr2:179454714;179454713;179454712
Novex-1	11640	35143;35144;35145	chr2:178589987;178589986;178589985	chr2:179454714;179454713;179454712
Novex-2	11707	35344;35345;35346	chr2:178589987;178589986;178589985	chr2:179454714;179454713;179454712
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-37
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5496
• 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
N/H	rs2049862820	None	0.001	N	0.085	0.121	0.165133752707	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/H	rs2049862820	None	0.001	N	0.085	0.121	0.165133752707	gnomAD-4.0.0	6.57523E-06	None	None	None	None	N	None	2.41255E-05	0	None	0	0	None	0	0	0	0	0
N/S	rs1470758075	0.232	None	N	0.045	0.119	0.117506650769	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	3.27E-05	None	0	0	0
N/S	rs1470758075	0.232	None	N	0.045	0.119	0.117506650769	gnomAD-4.0.0	1.36893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99664E-07	1.15964E-05	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
N/A	0.2061	likely_benign	0.2348	benign	-0.294	Destabilizing	0.055	N	0.307	neutral	None	None	None	None	N
N/C	0.3329	likely_benign	0.3174	benign	0.48	Stabilizing	0.883	D	0.323	neutral	None	None	None	None	N
N/D	0.1877	likely_benign	0.2348	benign	-0.059	Destabilizing	0.081	N	0.234	neutral	N	0.36069323	None	None	N
N/E	0.4959	ambiguous	0.5458	ambiguous	-0.106	Destabilizing	0.055	N	0.2	neutral	None	None	None	None	N
N/F	0.5607	ambiguous	0.5885	pathogenic	-0.702	Destabilizing	0.124	N	0.393	neutral	None	None	None	None	N
N/G	0.2623	likely_benign	0.317	benign	-0.454	Destabilizing	0.055	N	0.221	neutral	None	None	None	None	N
N/H	0.1315	likely_benign	0.1407	benign	-0.558	Destabilizing	0.001	N	0.085	neutral	N	0.477867117	None	None	N
N/I	0.4376	ambiguous	0.4297	ambiguous	0.042	Stabilizing	0.175	N	0.428	neutral	N	0.483062293	None	None	N
N/K	0.5213	ambiguous	0.5571	ambiguous	0.126	Stabilizing	0.042	N	0.201	neutral	N	0.458587923	None	None	N
N/L	0.3341	likely_benign	0.3452	ambiguous	0.042	Stabilizing	0.055	N	0.35	neutral	None	None	None	None	N
N/M	0.4066	ambiguous	0.4366	ambiguous	0.504	Stabilizing	0.859	D	0.333	neutral	None	None	None	None	N
N/P	0.8728	likely_pathogenic	0.855	pathogenic	-0.044	Destabilizing	0.667	D	0.388	neutral	None	None	None	None	N
N/Q	0.4062	ambiguous	0.4361	ambiguous	-0.299	Destabilizing	0.22	N	0.279	neutral	None	None	None	None	N
N/R	0.5195	ambiguous	0.5242	ambiguous	0.205	Stabilizing	0.22	N	0.189	neutral	None	None	None	None	N
N/S	0.0853	likely_benign	0.095	benign	-0.015	Destabilizing	None	N	0.045	neutral	N	0.43538299	None	None	N
N/T	0.1578	likely_benign	0.181	benign	0.068	Stabilizing	0.042	N	0.203	neutral	N	0.465956613	None	None	N
N/V	0.3458	ambiguous	0.356	ambiguous	-0.044	Destabilizing	0.22	N	0.392	neutral	None	None	None	None	N
N/W	0.8266	likely_pathogenic	0.84	pathogenic	-0.703	Destabilizing	0.667	D	0.33	neutral	None	None	None	None	N
N/Y	0.1638	likely_benign	0.1865	benign	-0.432	Destabilizing	None	N	0.114	neutral	N	0.426688935	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.