TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26142	78649;78650;78651	chr2:178567708;178567707;178567706	chr2:179432435;179432434;179432433
N2AB	24501	73726;73727;73728	chr2:178567708;178567707;178567706	chr2:179432435;179432434;179432433
N2A	23574	70945;70946;70947	chr2:178567708;178567707;178567706	chr2:179432435;179432434;179432433
N2B	17077	51454;51455;51456	chr2:178567708;178567707;178567706	chr2:179432435;179432434;179432433
Novex-1	17202	51829;51830;51831	chr2:178567708;178567707;178567706	chr2:179432435;179432434;179432433
Novex-2	17269	52030;52031;52032	chr2:178567708;178567707;178567706	chr2:179432435;179432434;179432433
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: Fn3-78
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3765
• 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/T	rs775124678	-0.149	0.919	N	0.494	0.396	0.267755039894	gnomAD-4.0.0	4.78722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.30231E-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	0.5616	ambiguous	0.5765	pathogenic	-0.68	Destabilizing	0.938	D	0.57	neutral	None	None	None	None	N
N/C	0.7189	likely_pathogenic	0.6931	pathogenic	0.174	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
N/D	0.5845	likely_pathogenic	0.5883	pathogenic	0.066	Stabilizing	0.958	D	0.427	neutral	N	0.517153437	None	None	N
N/E	0.9125	likely_pathogenic	0.9119	pathogenic	0.075	Stabilizing	0.968	D	0.547	neutral	None	None	None	None	N
N/F	0.9261	likely_pathogenic	0.9131	pathogenic	-0.812	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
N/G	0.6473	likely_pathogenic	0.6531	pathogenic	-0.914	Destabilizing	0.938	D	0.447	neutral	None	None	None	None	N
N/H	0.3782	ambiguous	0.3713	ambiguous	-0.855	Destabilizing	0.998	D	0.654	neutral	N	0.516500076	None	None	N
N/I	0.6405	likely_pathogenic	0.6188	pathogenic	-0.129	Destabilizing	0.994	D	0.822	deleterious	N	0.500338545	None	None	N
N/K	0.8914	likely_pathogenic	0.8935	pathogenic	0.014	Stabilizing	0.958	D	0.55	neutral	N	0.501221193	None	None	N
N/L	0.5741	likely_pathogenic	0.5691	pathogenic	-0.129	Destabilizing	0.991	D	0.757	deleterious	None	None	None	None	N
N/M	0.6766	likely_pathogenic	0.6593	pathogenic	0.368	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
N/P	0.788	likely_pathogenic	0.7839	pathogenic	-0.285	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
N/Q	0.8227	likely_pathogenic	0.8257	pathogenic	-0.562	Destabilizing	0.991	D	0.666	neutral	None	None	None	None	N
N/R	0.8792	likely_pathogenic	0.8757	pathogenic	0.035	Stabilizing	0.991	D	0.652	neutral	None	None	None	None	N
N/S	0.1542	likely_benign	0.1578	benign	-0.43	Destabilizing	0.234	N	0.256	neutral	N	0.510187392	None	None	N
N/T	0.3381	likely_benign	0.3483	ambiguous	-0.25	Destabilizing	0.919	D	0.494	neutral	N	0.496759522	None	None	N
N/V	0.5325	ambiguous	0.5204	ambiguous	-0.285	Destabilizing	0.991	D	0.806	deleterious	None	None	None	None	N
N/W	0.9687	likely_pathogenic	0.9619	pathogenic	-0.627	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
N/Y	0.5662	likely_pathogenic	0.5308	ambiguous	-0.416	Destabilizing	0.998	D	0.794	deleterious	N	0.491816897	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.