TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34210	102853;102854;102855	chr2:178533987;178533986;178533985	chr2:179398714;179398713;179398712
N2AB	32569	97930;97931;97932	chr2:178533987;178533986;178533985	chr2:179398714;179398713;179398712
N2A	31642	95149;95150;95151	chr2:178533987;178533986;178533985	chr2:179398714;179398713;179398712
N2B	25145	75658;75659;75660	chr2:178533987;178533986;178533985	chr2:179398714;179398713;179398712
Novex-1	25270	76033;76034;76035	chr2:178533987;178533986;178533985	chr2:179398714;179398713;179398712
Novex-2	25337	76234;76235;76236	chr2:178533987;178533986;178533985	chr2:179398714;179398713;179398712
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-160
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.203
• 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/N	None	None	1.0	D	0.814	0.38	0.280987212366	gnomAD-4.0.0	1.59104E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	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
K/A	0.914	likely_pathogenic	0.9022	pathogenic	-1.051	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
K/C	0.9621	likely_pathogenic	0.9628	pathogenic	-1.405	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
K/D	0.9777	likely_pathogenic	0.9759	pathogenic	-1.276	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
K/E	0.805	likely_pathogenic	0.772	pathogenic	-1.09	Destabilizing	0.999	D	0.666	neutral	N	0.477763622	None	None	N
K/F	0.9833	likely_pathogenic	0.9817	pathogenic	-0.61	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
K/G	0.9657	likely_pathogenic	0.9621	pathogenic	-1.465	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/H	0.7131	likely_pathogenic	0.7078	pathogenic	-1.783	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
K/I	0.8336	likely_pathogenic	0.8119	pathogenic	0.064	Stabilizing	1.0	D	0.913	deleterious	N	0.479881207	None	None	N
K/L	0.8406	likely_pathogenic	0.8319	pathogenic	0.064	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/M	0.7188	likely_pathogenic	0.6917	pathogenic	-0.159	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
K/N	0.9342	likely_pathogenic	0.9297	pathogenic	-1.399	Destabilizing	1.0	D	0.814	deleterious	D	0.536811925	None	None	N
K/P	0.998	likely_pathogenic	0.9983	pathogenic	-0.281	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
K/Q	0.5823	likely_pathogenic	0.5697	pathogenic	-1.348	Destabilizing	1.0	D	0.81	deleterious	N	0.493866438	None	None	N
K/R	0.1812	likely_benign	0.1848	benign	-1.116	Destabilizing	0.999	D	0.642	neutral	N	0.486383105	None	None	N
K/S	0.9324	likely_pathogenic	0.9228	pathogenic	-1.977	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
K/T	0.7299	likely_pathogenic	0.6914	pathogenic	-1.567	Destabilizing	1.0	D	0.835	deleterious	N	0.49044213	None	None	N
K/V	0.8022	likely_pathogenic	0.7776	pathogenic	-0.281	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
K/W	0.982	likely_pathogenic	0.9815	pathogenic	-0.581	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
K/Y	0.9556	likely_pathogenic	0.9492	pathogenic	-0.216	Destabilizing	1.0	D	0.903	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.