TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29830	89713;89714;89715	chr2:178553517;178553516;178553515	chr2:179418244;179418243;179418242
N2AB	28189	84790;84791;84792	chr2:178553517;178553516;178553515	chr2:179418244;179418243;179418242
N2A	27262	82009;82010;82011	chr2:178553517;178553516;178553515	chr2:179418244;179418243;179418242
N2B	20765	62518;62519;62520	chr2:178553517;178553516;178553515	chr2:179418244;179418243;179418242
Novex-1	20890	62893;62894;62895	chr2:178553517;178553516;178553515	chr2:179418244;179418243;179418242
Novex-2	20957	63094;63095;63096	chr2:178553517;178553516;178553515	chr2:179418244;179418243;179418242
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: Fn3-105
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.094
• 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	rs183476312	-1.908	0.891	N	0.792	0.151	None	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
A/T	rs183476312	-1.908	0.891	N	0.792	0.151	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None

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	0.6713	likely_pathogenic	0.7147	pathogenic	-2.131	Highly Destabilizing	0.996	D	0.81	deleterious	None	None	None	None	N
A/D	0.981	likely_pathogenic	0.9828	pathogenic	-2.622	Highly Destabilizing	0.891	D	0.821	deleterious	N	0.506803599	None	None	N
A/E	0.9508	likely_pathogenic	0.9554	pathogenic	-2.511	Highly Destabilizing	0.916	D	0.777	deleterious	None	None	None	None	N
A/F	0.9578	likely_pathogenic	0.9617	pathogenic	-1.091	Destabilizing	0.996	D	0.819	deleterious	None	None	None	None	N
A/G	0.4112	ambiguous	0.4196	ambiguous	-1.54	Destabilizing	0.7	D	0.575	neutral	N	0.494686825	None	None	N
A/H	0.9851	likely_pathogenic	0.9883	pathogenic	-1.569	Destabilizing	0.996	D	0.817	deleterious	None	None	None	None	N
A/I	0.6611	likely_pathogenic	0.7024	pathogenic	-0.338	Destabilizing	0.956	D	0.848	deleterious	None	None	None	None	N
A/K	0.9875	likely_pathogenic	0.9892	pathogenic	-1.374	Destabilizing	0.916	D	0.781	deleterious	None	None	None	None	N
A/L	0.6213	likely_pathogenic	0.6366	pathogenic	-0.338	Destabilizing	0.755	D	0.805	deleterious	None	None	None	None	N
A/M	0.7413	likely_pathogenic	0.7475	pathogenic	-0.877	Destabilizing	0.996	D	0.845	deleterious	None	None	None	None	N
A/N	0.9272	likely_pathogenic	0.9353	pathogenic	-1.661	Destabilizing	0.956	D	0.815	deleterious	None	None	None	None	N
A/P	0.2139	likely_benign	0.285	benign	-0.587	Destabilizing	0.017	N	0.429	neutral	N	0.493601787	None	None	N
A/Q	0.9401	likely_pathogenic	0.9465	pathogenic	-1.684	Destabilizing	0.956	D	0.839	deleterious	None	None	None	None	N
A/R	0.9724	likely_pathogenic	0.9739	pathogenic	-1.228	Destabilizing	0.956	D	0.848	deleterious	None	None	None	None	N
A/S	0.2813	likely_benign	0.3131	benign	-2.043	Highly Destabilizing	0.7	D	0.603	neutral	N	0.505282662	None	None	N
A/T	0.3575	ambiguous	0.3682	ambiguous	-1.823	Destabilizing	0.891	D	0.792	deleterious	N	0.470542183	None	None	N
A/V	0.2964	likely_benign	0.3307	benign	-0.587	Destabilizing	0.7	D	0.645	neutral	N	0.479090907	None	None	N
A/W	0.9944	likely_pathogenic	0.995	pathogenic	-1.551	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
A/Y	0.9812	likely_pathogenic	0.9834	pathogenic	-1.094	Destabilizing	0.996	D	0.83	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.