TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25102	75529;75530;75531	chr2:178570828;178570827;178570826	chr2:179435555;179435554;179435553
N2AB	23461	70606;70607;70608	chr2:178570828;178570827;178570826	chr2:179435555;179435554;179435553
N2A	22534	67825;67826;67827	chr2:178570828;178570827;178570826	chr2:179435555;179435554;179435553
N2B	16037	48334;48335;48336	chr2:178570828;178570827;178570826	chr2:179435555;179435554;179435553
Novex-1	16162	48709;48710;48711	chr2:178570828;178570827;178570826	chr2:179435555;179435554;179435553
Novex-2	16229	48910;48911;48912	chr2:178570828;178570827;178570826	chr2:179435555;179435554;179435553
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: Fn3-70
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0769
• 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	0.244	N	0.65	0.267	0.241664281697	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.5463	ambiguous	0.5383	ambiguous	-1.933	Destabilizing	0.958	D	0.766	deleterious	None	None	None	None	N
A/D	0.9949	likely_pathogenic	0.9922	pathogenic	-3.178	Highly Destabilizing	0.821	D	0.809	deleterious	N	0.50296376	None	None	N
A/E	0.9852	likely_pathogenic	0.9774	pathogenic	-3.005	Highly Destabilizing	0.858	D	0.739	deleterious	None	None	None	None	N
A/F	0.9469	likely_pathogenic	0.9259	pathogenic	-0.757	Destabilizing	0.749	D	0.803	deleterious	None	None	None	None	N
A/G	0.5745	likely_pathogenic	0.5142	ambiguous	-1.735	Destabilizing	0.566	D	0.553	neutral	N	0.502710271	None	None	N
A/H	0.9917	likely_pathogenic	0.9889	pathogenic	-1.822	Destabilizing	0.986	D	0.805	deleterious	None	None	None	None	N
A/I	0.5064	ambiguous	0.4503	ambiguous	-0.311	Destabilizing	0.128	N	0.735	deleterious	None	None	None	None	N
A/K	0.9942	likely_pathogenic	0.991	pathogenic	-1.445	Destabilizing	0.858	D	0.759	deleterious	None	None	None	None	N
A/L	0.5624	ambiguous	0.4954	ambiguous	-0.311	Destabilizing	0.299	N	0.635	neutral	None	None	None	None	N
A/M	0.6566	likely_pathogenic	0.5911	pathogenic	-0.875	Destabilizing	0.919	D	0.832	deleterious	None	None	None	None	N
A/N	0.9622	likely_pathogenic	0.9481	pathogenic	-1.9	Destabilizing	0.949	D	0.804	deleterious	None	None	None	None	N
A/P	0.7916	likely_pathogenic	0.7205	pathogenic	-0.621	Destabilizing	0.933	D	0.803	deleterious	N	0.473081445	None	None	N
A/Q	0.9687	likely_pathogenic	0.9595	pathogenic	-1.758	Destabilizing	0.949	D	0.812	deleterious	None	None	None	None	N
A/R	0.9819	likely_pathogenic	0.9767	pathogenic	-1.424	Destabilizing	0.858	D	0.806	deleterious	None	None	None	None	N
A/S	0.3114	likely_benign	0.2755	benign	-2.17	Highly Destabilizing	0.392	N	0.61	neutral	N	0.490846986	None	None	N
A/T	0.2956	likely_benign	0.2418	benign	-1.895	Destabilizing	0.244	N	0.65	prob.neutral	N	0.47002048	None	None	N
A/V	0.203	likely_benign	0.1742	benign	-0.621	Destabilizing	0.005	N	0.331	neutral	N	0.469540344	None	None	N
A/W	0.9969	likely_pathogenic	0.9951	pathogenic	-1.433	Destabilizing	0.986	D	0.801	deleterious	None	None	None	None	N
A/Y	0.9871	likely_pathogenic	0.9817	pathogenic	-1.016	Destabilizing	0.858	D	0.798	deleterious	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.