TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10029	30310;30311;30312	chr2:178704285;178704284;178704283	chr2:179569012;179569011;179569010
N2AB	9712	29359;29360;29361	chr2:178704285;178704284;178704283	chr2:179569012;179569011;179569010
N2A	8785	26578;26579;26580	chr2:178704285;178704284;178704283	chr2:179569012;179569011;179569010
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-85
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.5539
• 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
K/Q	None	None	0.045	None	0.182	0.142	0.206339911435	gnomAD-4.0.0	1.36827E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31863E-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
K/A	0.6323	likely_pathogenic	0.6074	pathogenic	0.014	Stabilizing	0.4	N	0.293	neutral	None	None	None	None	N
K/C	0.9118	likely_pathogenic	0.9301	pathogenic	-0.471	Destabilizing	0.992	D	0.429	neutral	None	None	None	None	N
K/D	0.8483	likely_pathogenic	0.8161	pathogenic	-0.296	Destabilizing	0.447	N	0.301	neutral	None	None	None	None	N
K/E	0.3826	ambiguous	0.3375	benign	-0.283	Destabilizing	0.001	N	0.114	neutral	None	None	None	None	N
K/F	0.8747	likely_pathogenic	0.8677	pathogenic	-0.245	Destabilizing	0.972	D	0.395	neutral	None	None	None	None	N
K/G	0.8085	likely_pathogenic	0.7988	pathogenic	-0.148	Destabilizing	0.617	D	0.345	neutral	None	None	None	None	N
K/H	0.4219	ambiguous	0.4275	ambiguous	-0.248	Destabilizing	0.92	D	0.327	neutral	None	None	None	None	N
K/I	0.5375	ambiguous	0.494	ambiguous	0.364	Stabilizing	0.896	D	0.403	neutral	None	None	None	None	N
K/L	0.4903	ambiguous	0.471	ambiguous	0.364	Stabilizing	0.617	D	0.36	neutral	None	None	None	None	N
K/M	0.4185	ambiguous	0.3859	ambiguous	-0.163	Destabilizing	0.972	D	0.323	neutral	None	None	None	None	N
K/N	0.6547	likely_pathogenic	0.6062	pathogenic	-0.084	Destabilizing	0.549	D	0.319	neutral	None	None	None	None	N
K/P	0.7279	likely_pathogenic	0.7401	pathogenic	0.272	Stabilizing	0.92	D	0.306	neutral	None	None	None	None	N
K/Q	0.189	likely_benign	0.1841	benign	-0.167	Destabilizing	0.045	N	0.182	neutral	None	None	None	None	N
K/R	0.126	likely_benign	0.1243	benign	-0.129	Destabilizing	0.004	N	0.214	neutral	None	None	None	None	N
K/S	0.685	likely_pathogenic	0.6563	pathogenic	-0.406	Destabilizing	0.617	D	0.279	neutral	None	None	None	None	N
K/T	0.35	ambiguous	0.321	benign	-0.264	Destabilizing	0.549	D	0.311	neutral	None	None	None	None	N
K/V	0.5476	ambiguous	0.514	ambiguous	0.272	Stabilizing	0.766	D	0.349	neutral	None	None	None	None	N
K/W	0.8853	likely_pathogenic	0.8928	pathogenic	-0.373	Destabilizing	0.992	D	0.462	neutral	None	None	None	None	N
K/Y	0.755	likely_pathogenic	0.7428	pathogenic	-0.022	Destabilizing	0.972	D	0.375	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.