TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15269	46030;46031;46032	chr2:178620805;178620804;178620803	chr2:179485532;179485531;179485530
N2AB	13628	41107;41108;41109	chr2:178620805;178620804;178620803	chr2:179485532;179485531;179485530
N2A	12701	38326;38327;38328	chr2:178620805;178620804;178620803	chr2:179485532;179485531;179485530
N2B	6204	18835;18836;18837	chr2:178620805;178620804;178620803	chr2:179485532;179485531;179485530
Novex-1	6329	19210;19211;19212	chr2:178620805;178620804;178620803	chr2:179485532;179485531;179485530
Novex-2	6396	19411;19412;19413	chr2:178620805;178620804;178620803	chr2:179485532;179485531;179485530
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-104
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0847
• 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
A/P	None	None	0.949	D	0.687	0.546	0.605722390383	gnomAD-4.0.0	1.59334E-06	None	None	None	None	N	None	0	0	None	0	2.77685E-05	None	0	0	0	0	0
A/V	rs1576550520	None	0.075	N	0.375	0.231	0.435152311215	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86266E-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
A/C	0.5519	ambiguous	0.6099	pathogenic	-1.464	Destabilizing	0.996	D	0.616	neutral	None	None	None	None	N
A/D	0.9647	likely_pathogenic	0.9694	pathogenic	-3.06	Highly Destabilizing	0.923	D	0.695	prob.neutral	None	None	None	None	N
A/E	0.9475	likely_pathogenic	0.9544	pathogenic	-2.968	Highly Destabilizing	0.901	D	0.675	neutral	D	0.65851299	None	None	N
A/F	0.8201	likely_pathogenic	0.8513	pathogenic	-0.737	Destabilizing	0.961	D	0.697	prob.neutral	None	None	None	None	N
A/G	0.3509	ambiguous	0.3591	ambiguous	-1.41	Destabilizing	0.565	D	0.566	neutral	D	0.658410533	None	None	N
A/H	0.9639	likely_pathogenic	0.9703	pathogenic	-1.568	Destabilizing	0.989	D	0.686	prob.neutral	None	None	None	None	N
A/I	0.3897	ambiguous	0.4846	ambiguous	-0.24	Destabilizing	0.633	D	0.654	neutral	None	None	None	None	N
A/K	0.9713	likely_pathogenic	0.9735	pathogenic	-1.402	Destabilizing	0.858	D	0.681	prob.neutral	None	None	None	None	N
A/L	0.3517	ambiguous	0.4212	ambiguous	-0.24	Destabilizing	0.633	D	0.573	neutral	None	None	None	None	N
A/M	0.4602	ambiguous	0.5722	pathogenic	-0.405	Destabilizing	0.989	D	0.667	neutral	None	None	None	None	N
A/N	0.8549	likely_pathogenic	0.8964	pathogenic	-1.685	Destabilizing	0.858	D	0.698	prob.neutral	None	None	None	None	N
A/P	0.7388	likely_pathogenic	0.7917	pathogenic	-0.485	Destabilizing	0.949	D	0.687	prob.neutral	D	0.594926132	None	None	N
A/Q	0.9305	likely_pathogenic	0.9374	pathogenic	-1.661	Destabilizing	0.923	D	0.681	prob.neutral	None	None	None	None	N
A/R	0.9391	likely_pathogenic	0.9376	pathogenic	-1.233	Destabilizing	0.923	D	0.699	prob.neutral	None	None	None	None	N
A/S	0.1965	likely_benign	0.2259	benign	-1.863	Destabilizing	0.034	N	0.379	neutral	N	0.516281361	None	None	N
A/T	0.107	likely_benign	0.1697	benign	-1.695	Destabilizing	0.034	N	0.325	neutral	N	0.507817585	None	None	N
A/V	0.1744	likely_benign	0.2166	benign	-0.485	Destabilizing	0.075	N	0.375	neutral	N	0.490406781	None	None	N
A/W	0.9857	likely_pathogenic	0.9876	pathogenic	-1.413	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
A/Y	0.9499	likely_pathogenic	0.9589	pathogenic	-1.013	Destabilizing	0.987	D	0.702	prob.neutral	None	None	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.