TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32191	96796;96797;96798	chr2:178543402;178543401;178543400	chr2:179408129;179408128;179408127
N2AB	30550	91873;91874;91875	chr2:178543402;178543401;178543400	chr2:179408129;179408128;179408127
N2A	29623	89092;89093;89094	chr2:178543402;178543401;178543400	chr2:179408129;179408128;179408127
N2B	23126	69601;69602;69603	chr2:178543402;178543401;178543400	chr2:179408129;179408128;179408127
Novex-1	23251	69976;69977;69978	chr2:178543402;178543401;178543400	chr2:179408129;179408128;179408127
Novex-2	23318	70177;70178;70179	chr2:178543402;178543401;178543400	chr2:179408129;179408128;179408127
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-122
• Domain position: 87
• Structural Position: 121
• Q(SASA): 0.1544
• 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
C/R	None	None	0.999	N	0.836	0.357	0.674546049349	gnomAD-4.0.0	2.05262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69838E-06	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
C/A	0.2418	likely_benign	0.2317	benign	-1.803	Destabilizing	0.995	D	0.712	prob.delet.	None	None	None	None	N
C/D	0.7557	likely_pathogenic	0.7097	pathogenic	-1.211	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
C/E	0.7439	likely_pathogenic	0.699	pathogenic	-1.077	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
C/F	0.2499	likely_benign	0.2119	benign	-1.092	Destabilizing	0.999	D	0.793	deleterious	N	0.471045481	None	None	N
C/G	0.1838	likely_benign	0.1811	benign	-2.129	Highly Destabilizing	0.999	D	0.77	deleterious	N	0.451693662	None	None	N
C/H	0.4847	ambiguous	0.4264	ambiguous	-2.279	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
C/I	0.4992	ambiguous	0.4246	ambiguous	-0.948	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
C/K	0.6749	likely_pathogenic	0.614	pathogenic	-1.496	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
C/L	0.4484	ambiguous	0.3988	ambiguous	-0.948	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
C/M	0.5348	ambiguous	0.4886	ambiguous	0.089	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
C/N	0.4984	ambiguous	0.4694	ambiguous	-1.572	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
C/P	0.9859	likely_pathogenic	0.9762	pathogenic	-1.208	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
C/Q	0.4609	ambiguous	0.4101	ambiguous	-1.42	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
C/R	0.322	likely_benign	0.2709	benign	-1.433	Destabilizing	0.999	D	0.836	deleterious	N	0.509413814	None	None	N
C/S	0.2073	likely_benign	0.1952	benign	-2.019	Highly Destabilizing	0.999	D	0.735	deleterious	N	0.401637696	None	None	N
C/T	0.3356	likely_benign	0.3211	benign	-1.716	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
C/V	0.3444	ambiguous	0.3005	benign	-1.208	Destabilizing	0.998	D	0.722	deleterious	None	None	None	None	N
C/W	0.6149	likely_pathogenic	0.5184	ambiguous	-1.24	Destabilizing	1.0	D	0.814	deleterious	N	0.483162255	None	None	N
C/Y	0.3519	ambiguous	0.3037	benign	-1.186	Destabilizing	0.999	D	0.833	deleterious	N	0.509413814	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.