TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17388	52387;52388;52389	chr2:178608849;178608848;178608847	chr2:179473576;179473575;179473574
N2AB	15747	47464;47465;47466	chr2:178608849;178608848;178608847	chr2:179473576;179473575;179473574
N2A	14820	44683;44684;44685	chr2:178608849;178608848;178608847	chr2:179473576;179473575;179473574
N2B	8323	25192;25193;25194	chr2:178608849;178608848;178608847	chr2:179473576;179473575;179473574
Novex-1	8448	25567;25568;25569	chr2:178608849;178608848;178608847	chr2:179473576;179473575;179473574
Novex-2	8515	25768;25769;25770	chr2:178608849;178608848;178608847	chr2:179473576;179473575;179473574
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: Fn3-14
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0502
• 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	None	None	1.0	N	0.791	0.517	0.628884166652	gnomAD-4.0.0	1.59485E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.90505E-05	0	0	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
C/A	0.8488	likely_pathogenic	0.8252	pathogenic	0.044	Stabilizing	0.998	D	0.646	neutral	None	None	None	None	N
C/D	0.9997	likely_pathogenic	0.9996	pathogenic	-1.014	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
C/E	0.9997	likely_pathogenic	0.9996	pathogenic	-0.76	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
C/F	0.8046	likely_pathogenic	0.7915	pathogenic	0.247	Stabilizing	1.0	D	0.921	deleterious	N	0.4710875	None	None	N
C/G	0.8197	likely_pathogenic	0.7699	pathogenic	-0.264	Destabilizing	1.0	D	0.893	deleterious	N	0.501583765	None	None	N
C/H	0.9983	likely_pathogenic	0.9978	pathogenic	-0.71	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
C/I	0.7132	likely_pathogenic	0.6901	pathogenic	0.873	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
C/K	0.9998	likely_pathogenic	0.9997	pathogenic	0.574	Stabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
C/L	0.5407	ambiguous	0.5165	ambiguous	0.873	Stabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
C/M	0.8689	likely_pathogenic	0.8595	pathogenic	0.105	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
C/N	0.9978	likely_pathogenic	0.9973	pathogenic	-0.449	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
C/P	0.9977	likely_pathogenic	0.9967	pathogenic	0.617	Stabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
C/Q	0.9989	likely_pathogenic	0.9985	pathogenic	0.18	Stabilizing	1.0	D	0.944	deleterious	None	None	None	None	N
C/R	0.9983	likely_pathogenic	0.9975	pathogenic	-0.457	Destabilizing	1.0	D	0.935	deleterious	N	0.501583765	None	None	N
C/S	0.9641	likely_pathogenic	0.9528	pathogenic	-0.323	Destabilizing	1.0	D	0.791	deleterious	N	0.501583765	None	None	N
C/T	0.962	likely_pathogenic	0.9524	pathogenic	0.094	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
C/V	0.5858	likely_pathogenic	0.5637	ambiguous	0.617	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
C/W	0.9916	likely_pathogenic	0.9893	pathogenic	-0.255	Destabilizing	1.0	D	0.906	deleterious	N	0.501583765	None	None	N
C/Y	0.9751	likely_pathogenic	0.9704	pathogenic	0.11	Stabilizing	1.0	D	0.938	deleterious	N	0.501583765	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.