TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16016	48271;48272;48273	chr2:178616843;178616842;178616841	chr2:179481570;179481569;179481568
N2AB	14375	43348;43349;43350	chr2:178616843;178616842;178616841	chr2:179481570;179481569;179481568
N2A	13448	40567;40568;40569	chr2:178616843;178616842;178616841	chr2:179481570;179481569;179481568
N2B	6951	21076;21077;21078	chr2:178616843;178616842;178616841	chr2:179481570;179481569;179481568
Novex-1	7076	21451;21452;21453	chr2:178616843;178616842;178616841	chr2:179481570;179481569;179481568
Novex-2	7143	21652;21653;21654	chr2:178616843;178616842;178616841	chr2:179481570;179481569;179481568
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-109
• Domain position: 49
• Structural Position: 134
• Q(SASA): 0.2894
• 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/T	None	None	0.046	N	0.147	0.112	0.271763555656	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.4168	ambiguous	0.4317	ambiguous	-0.874	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	N
A/D	0.3114	likely_benign	0.4035	ambiguous	-0.077	Destabilizing	0.968	D	0.635	neutral	N	0.437569351	None	None	N
A/E	0.2985	likely_benign	0.3881	ambiguous	-0.168	Destabilizing	0.919	D	0.533	neutral	None	None	None	None	N
A/F	0.4539	ambiguous	0.4976	ambiguous	-0.909	Destabilizing	0.988	D	0.691	prob.neutral	None	None	None	None	N
A/G	0.1523	likely_benign	0.172	benign	-0.711	Destabilizing	0.811	D	0.425	neutral	N	0.481305799	None	None	N
A/H	0.4542	ambiguous	0.5031	ambiguous	-0.745	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
A/I	0.3577	ambiguous	0.4032	ambiguous	-0.321	Destabilizing	0.976	D	0.546	neutral	None	None	None	None	N
A/K	0.4131	ambiguous	0.4918	ambiguous	-0.687	Destabilizing	0.919	D	0.531	neutral	None	None	None	None	N
A/L	0.255	likely_benign	0.2909	benign	-0.321	Destabilizing	0.851	D	0.51	neutral	None	None	None	None	N
A/M	0.3345	likely_benign	0.3697	ambiguous	-0.404	Destabilizing	0.999	D	0.586	neutral	None	None	None	None	N
A/N	0.2391	likely_benign	0.2697	benign	-0.405	Destabilizing	0.976	D	0.635	neutral	None	None	None	None	N
A/P	0.3408	ambiguous	0.3585	ambiguous	-0.361	Destabilizing	0.984	D	0.559	neutral	N	0.51597344	None	None	N
A/Q	0.3497	ambiguous	0.3898	ambiguous	-0.569	Destabilizing	0.988	D	0.597	neutral	None	None	None	None	N
A/R	0.3502	ambiguous	0.4196	ambiguous	-0.371	Destabilizing	0.976	D	0.587	neutral	None	None	None	None	N
A/S	0.0928	likely_benign	0.0974	benign	-0.787	Destabilizing	0.103	N	0.187	neutral	N	0.491258547	None	None	N
A/T	0.0967	likely_benign	0.1113	benign	-0.768	Destabilizing	0.046	N	0.147	neutral	N	0.389967517	None	None	N
A/V	0.1891	likely_benign	0.2171	benign	-0.361	Destabilizing	0.811	D	0.451	neutral	N	0.500175168	None	None	N
A/W	0.7398	likely_pathogenic	0.7771	pathogenic	-1.099	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
A/Y	0.4691	ambiguous	0.5093	ambiguous	-0.721	Destabilizing	0.996	D	0.7	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.