TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27796	83611;83612;83613	chr2:178562746;178562745;178562744	chr2:179427473;179427472;179427471
N2AB	26155	78688;78689;78690	chr2:178562746;178562745;178562744	chr2:179427473;179427472;179427471
N2A	25228	75907;75908;75909	chr2:178562746;178562745;178562744	chr2:179427473;179427472;179427471
N2B	18731	56416;56417;56418	chr2:178562746;178562745;178562744	chr2:179427473;179427472;179427471
Novex-1	18856	56791;56792;56793	chr2:178562746;178562745;178562744	chr2:179427473;179427472;179427471
Novex-2	18923	56992;56993;56994	chr2:178562746;178562745;178562744	chr2:179427473;179427472;179427471
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-90
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1453
• 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
A/G	rs368241592	-1.417	0.919	N	0.6	0.357	0.355450299083	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
A/G	rs368241592	-1.417	0.919	N	0.6	0.357	0.355450299083	gnomAD-4.0.0	6.85141E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00325E-07	0	0
A/T	rs780507493	-1.154	0.919	N	0.673	0.201	0.342631996419	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
A/T	rs780507493	-1.154	0.919	N	0.673	0.201	0.342631996419	gnomAD-4.0.0	6.38439E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88558E-05	0	8.59949E-06	0	0
A/V	rs368241592	-0.615	0.958	N	0.749	0.367	None	gnomAD-2.1.1	2.02E-05	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	1.31484E-04	None	0	0	0
A/V	rs368241592	-0.615	0.958	N	0.749	0.367	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	4.14079E-04	0
A/V	rs368241592	-0.615	0.958	N	0.749	0.367	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
A/V	rs368241592	-0.615	0.958	N	0.749	0.367	None	gnomAD-4.0.0	9.30655E-06	None	None	None	None	I	None	2.67158E-05	0	None	0	0	None	0	0	1.69676E-06	1.10074E-04	1.60359E-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
A/C	0.5494	ambiguous	0.5016	ambiguous	-0.798	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
A/D	0.7903	likely_pathogenic	0.7418	pathogenic	-1.089	Destabilizing	0.988	D	0.834	deleterious	N	0.50980339	None	None	I
A/E	0.7702	likely_pathogenic	0.7316	pathogenic	-1.154	Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	I
A/F	0.7393	likely_pathogenic	0.6734	pathogenic	-1.148	Destabilizing	0.995	D	0.852	deleterious	None	None	None	None	I
A/G	0.26	likely_benign	0.2303	benign	-1.147	Destabilizing	0.919	D	0.6	neutral	N	0.503333204	None	None	I
A/H	0.8301	likely_pathogenic	0.7986	pathogenic	-1.257	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
A/I	0.7196	likely_pathogenic	0.6253	pathogenic	-0.501	Destabilizing	0.995	D	0.83	deleterious	None	None	None	None	I
A/K	0.9192	likely_pathogenic	0.8998	pathogenic	-1.113	Destabilizing	0.991	D	0.805	deleterious	None	None	None	None	I
A/L	0.5033	ambiguous	0.4602	ambiguous	-0.501	Destabilizing	0.968	D	0.764	deleterious	None	None	None	None	I
A/M	0.4968	ambiguous	0.4395	ambiguous	-0.324	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
A/N	0.6279	likely_pathogenic	0.561	ambiguous	-0.75	Destabilizing	0.991	D	0.841	deleterious	None	None	None	None	I
A/P	0.9876	likely_pathogenic	0.9855	pathogenic	-0.603	Destabilizing	0.994	D	0.827	deleterious	N	0.499970425	None	None	I
A/Q	0.7127	likely_pathogenic	0.6877	pathogenic	-0.972	Destabilizing	0.991	D	0.831	deleterious	None	None	None	None	I
A/R	0.8752	likely_pathogenic	0.8611	pathogenic	-0.696	Destabilizing	0.991	D	0.825	deleterious	None	None	None	None	I
A/S	0.0929	likely_benign	0.0859	benign	-1.08	Destabilizing	0.234	N	0.472	neutral	N	0.393688296	None	None	I
A/T	0.1865	likely_benign	0.1533	benign	-1.058	Destabilizing	0.919	D	0.673	neutral	N	0.497932958	None	None	I
A/V	0.3558	ambiguous	0.2891	benign	-0.603	Destabilizing	0.958	D	0.749	deleterious	N	0.475736878	None	None	I
A/W	0.9605	likely_pathogenic	0.948	pathogenic	-1.419	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
A/Y	0.8417	likely_pathogenic	0.8004	pathogenic	-1.049	Destabilizing	0.998	D	0.851	deleterious	None	None	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.