TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3260	10003;10004;10005	chr2:178764737;178764736;178764735	chr2:179629464;179629463;179629462
N2AB	3260	10003;10004;10005	chr2:178764737;178764736;178764735	chr2:179629464;179629463;179629462
N2A	3260	10003;10004;10005	chr2:178764737;178764736;178764735	chr2:179629464;179629463;179629462
N2B	3214	9865;9866;9867	chr2:178764737;178764736;178764735	chr2:179629464;179629463;179629462
Novex-1	3214	9865;9866;9867	chr2:178764737;178764736;178764735	chr2:179629464;179629463;179629462
Novex-2	3214	9865;9866;9867	chr2:178764737;178764736;178764735	chr2:179629464;179629463;179629462
Novex-3	3260	10003;10004;10005	chr2:178764737;178764736;178764735	chr2:179629464;179629463;179629462

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-23
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1093
• 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/P	None	None	0.949	D	0.812	0.573	0.519728874731	gnomAD-4.0.0	1.5907E-06	None	None	None	None	N	None	0	2.28686E-05	None	0	0	None	0	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
A/C	0.4903	ambiguous	0.5961	pathogenic	-1.298	Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	N
A/D	0.9696	likely_pathogenic	0.9944	pathogenic	-2.701	Highly Destabilizing	0.901	D	0.845	deleterious	D	0.602232862	None	None	N
A/E	0.9491	likely_pathogenic	0.9886	pathogenic	-2.555	Highly Destabilizing	0.923	D	0.823	deleterious	None	None	None	None	N
A/F	0.8211	likely_pathogenic	0.933	pathogenic	-0.891	Destabilizing	0.961	D	0.861	deleterious	None	None	None	None	N
A/G	0.2971	likely_benign	0.479	ambiguous	-1.752	Destabilizing	0.722	D	0.698	prob.neutral	D	0.522336766	None	None	N
A/H	0.9623	likely_pathogenic	0.9893	pathogenic	-2.122	Highly Destabilizing	0.996	D	0.871	deleterious	None	None	None	None	N
A/I	0.4405	ambiguous	0.6469	pathogenic	-0.222	Destabilizing	0.633	D	0.777	deleterious	None	None	None	None	N
A/K	0.9799	likely_pathogenic	0.9959	pathogenic	-1.592	Destabilizing	0.923	D	0.83	deleterious	None	None	None	None	N
A/L	0.4009	ambiguous	0.6036	pathogenic	-0.222	Destabilizing	0.415	N	0.764	deleterious	None	None	None	None	N
A/M	0.3804	ambiguous	0.6399	pathogenic	-0.328	Destabilizing	0.961	D	0.817	deleterious	None	None	None	None	N
A/N	0.8693	likely_pathogenic	0.9695	pathogenic	-1.744	Destabilizing	0.923	D	0.859	deleterious	None	None	None	None	N
A/P	0.944	likely_pathogenic	0.9882	pathogenic	-0.552	Destabilizing	0.949	D	0.812	deleterious	D	0.602232862	None	None	N
A/Q	0.9323	likely_pathogenic	0.9775	pathogenic	-1.646	Destabilizing	0.961	D	0.805	deleterious	None	None	None	None	N
A/R	0.9573	likely_pathogenic	0.9884	pathogenic	-1.473	Destabilizing	0.923	D	0.817	deleterious	None	None	None	None	N
A/S	0.1708	likely_benign	0.2585	benign	-2.089	Highly Destabilizing	0.565	D	0.685	prob.neutral	D	0.52205691	None	None	N
A/T	0.0864	likely_benign	0.1621	benign	-1.845	Destabilizing	0.008	N	0.433	neutral	N	0.503267325	None	None	N
A/V	0.1594	likely_benign	0.2381	benign	-0.552	Destabilizing	0.014	N	0.395	neutral	N	0.447376094	None	None	N
A/W	0.9845	likely_pathogenic	0.9965	pathogenic	-1.646	Destabilizing	0.996	D	0.883	deleterious	None	None	None	None	N
A/Y	0.9439	likely_pathogenic	0.9838	pathogenic	-1.168	Destabilizing	0.987	D	0.859	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.