TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5720	17383;17384;17385	chr2:178731717;178731716;178731715	chr2:179596444;179596443;179596442
N2AB	5403	16432;16433;16434	chr2:178731717;178731716;178731715	chr2:179596444;179596443;179596442
N2A	4476	13651;13652;13653	chr2:178731717;178731716;178731715	chr2:179596444;179596443;179596442
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-40
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.0906
• 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/G	rs748067586	-2.114	0.03	N	0.564	0.259	0.733364837216	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.31053E-04	None	0	0	0
C/G	rs748067586	-2.114	0.03	N	0.564	0.259	0.733364837216	gnomAD-4.0.0	4.7942E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.9625E-05	1.6581E-05

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	0.4538	ambiguous	0.4082	ambiguous	-1.829	Destabilizing	0.864	D	0.56	neutral	None	None	None	None	N
C/D	0.8626	likely_pathogenic	0.8402	pathogenic	-0.408	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	N
C/E	0.9376	likely_pathogenic	0.9201	pathogenic	-0.236	Destabilizing	0.991	D	0.808	deleterious	None	None	None	None	N
C/F	0.4611	ambiguous	0.4284	ambiguous	-1.081	Destabilizing	0.998	D	0.792	deleterious	N	0.500113735	None	None	N
C/G	0.2286	likely_benign	0.21	benign	-2.181	Highly Destabilizing	0.03	N	0.564	neutral	N	0.486124083	None	None	N
C/H	0.756	likely_pathogenic	0.7174	pathogenic	-2.062	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
C/I	0.6987	likely_pathogenic	0.6261	pathogenic	-0.893	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
C/K	0.9331	likely_pathogenic	0.9156	pathogenic	-0.773	Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
C/L	0.6627	likely_pathogenic	0.5778	pathogenic	-0.893	Destabilizing	0.984	D	0.769	deleterious	None	None	None	None	N
C/M	0.8337	likely_pathogenic	0.7765	pathogenic	0.169	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
C/N	0.7095	likely_pathogenic	0.6633	pathogenic	-1.056	Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
C/P	0.9864	likely_pathogenic	0.9834	pathogenic	-1.181	Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
C/Q	0.8334	likely_pathogenic	0.7909	pathogenic	-0.779	Destabilizing	0.995	D	0.824	deleterious	None	None	None	None	N
C/R	0.6856	likely_pathogenic	0.6537	pathogenic	-0.88	Destabilizing	0.994	D	0.827	deleterious	D	0.529613807	None	None	N
C/S	0.2701	likely_benign	0.2434	benign	-1.594	Destabilizing	0.476	N	0.568	neutral	N	0.4722963	None	None	N
C/T	0.4552	ambiguous	0.3953	ambiguous	-1.218	Destabilizing	0.939	D	0.764	deleterious	None	None	None	None	N
C/V	0.5903	likely_pathogenic	0.5243	ambiguous	-1.181	Destabilizing	0.984	D	0.778	deleterious	None	None	None	None	N
C/W	0.8396	likely_pathogenic	0.8094	pathogenic	-1.143	Destabilizing	0.999	D	0.773	deleterious	N	0.507457569	None	None	N
C/Y	0.635	likely_pathogenic	0.5816	pathogenic	-1.096	Destabilizing	0.998	D	0.793	deleterious	N	0.495594285	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.