TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4783	14572;14573;14574	chr2:178738106;178738105;178738104	chr2:179602833;179602832;179602831
N2AB	4466	13621;13622;13623	chr2:178738106;178738105;178738104	chr2:179602833;179602832;179602831
N2A	3539	10840;10841;10842	chr2:178738106;178738105;178738104	chr2:179602833;179602832;179602831
N2B	4420	13483;13484;13485	chr2:178738106;178738105;178738104	chr2:179602833;179602832;179602831
Novex-1	4545	13858;13859;13860	chr2:178738106;178738105;178738104	chr2:179602833;179602832;179602831
Novex-2	4612	14059;14060;14061	chr2:178738106;178738105;178738104	chr2:179602833;179602832;179602831
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-30
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1539
• 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
C/S	rs748913179	-1.46	0.046	N	0.478	0.258	0.547384771329	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
C/S	rs748913179	-1.46	0.046	N	0.478	0.258	0.547384771329	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-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
C/A	0.4763	ambiguous	0.4343	ambiguous	-1.675	Destabilizing	0.702	D	0.595	neutral	None	None	None	None	N
C/D	0.7983	likely_pathogenic	0.8518	pathogenic	-0.347	Destabilizing	0.976	D	0.831	deleterious	None	None	None	None	N
C/E	0.9233	likely_pathogenic	0.9421	pathogenic	-0.277	Destabilizing	0.976	D	0.83	deleterious	None	None	None	None	N
C/F	0.5403	ambiguous	0.5501	ambiguous	-1.147	Destabilizing	0.995	D	0.81	deleterious	D	0.545431868	None	None	N
C/G	0.294	likely_benign	0.289	benign	-1.955	Destabilizing	0.811	D	0.821	deleterious	N	0.5112759	None	None	N
C/H	0.8317	likely_pathogenic	0.8319	pathogenic	-1.985	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
C/I	0.7832	likely_pathogenic	0.7984	pathogenic	-0.966	Destabilizing	0.988	D	0.831	deleterious	None	None	None	None	N
C/K	0.9745	likely_pathogenic	0.9747	pathogenic	-0.92	Destabilizing	0.976	D	0.834	deleterious	None	None	None	None	N
C/L	0.7511	likely_pathogenic	0.7405	pathogenic	-0.966	Destabilizing	0.919	D	0.792	deleterious	None	None	None	None	N
C/M	0.8011	likely_pathogenic	0.7928	pathogenic	-0.093	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
C/N	0.6965	likely_pathogenic	0.7096	pathogenic	-0.772	Destabilizing	0.976	D	0.829	deleterious	None	None	None	None	N
C/P	0.9955	likely_pathogenic	0.9954	pathogenic	-1.177	Destabilizing	0.988	D	0.851	deleterious	None	None	None	None	N
C/Q	0.8734	likely_pathogenic	0.879	pathogenic	-0.773	Destabilizing	0.988	D	0.859	deleterious	None	None	None	None	N
C/R	0.8629	likely_pathogenic	0.8658	pathogenic	-0.71	Destabilizing	0.968	D	0.856	deleterious	N	0.505985962	None	None	N
C/S	0.2041	likely_benign	0.1928	benign	-1.319	Destabilizing	0.046	N	0.478	neutral	N	0.460136404	None	None	N
C/T	0.3995	ambiguous	0.3566	ambiguous	-1.079	Destabilizing	0.851	D	0.791	deleterious	None	None	None	None	N
C/V	0.6384	likely_pathogenic	0.6329	pathogenic	-1.177	Destabilizing	0.919	D	0.817	deleterious	None	None	None	None	N
C/W	0.8693	likely_pathogenic	0.8778	pathogenic	-1.099	Destabilizing	0.999	D	0.783	deleterious	N	0.507979455	None	None	N
C/Y	0.72	likely_pathogenic	0.7266	pathogenic	-1.088	Destabilizing	0.995	D	0.817	deleterious	N	0.511408116	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.