TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26965	81118;81119;81120	chr2:178565239;178565238;178565237	chr2:179429966;179429965;179429964
N2AB	25324	76195;76196;76197	chr2:178565239;178565238;178565237	chr2:179429966;179429965;179429964
N2A	24397	73414;73415;73416	chr2:178565239;178565238;178565237	chr2:179429966;179429965;179429964
N2B	17900	53923;53924;53925	chr2:178565239;178565238;178565237	chr2:179429966;179429965;179429964
Novex-1	18025	54298;54299;54300	chr2:178565239;178565238;178565237	chr2:179429966;179429965;179429964
Novex-2	18092	54499;54500;54501	chr2:178565239;178565238;178565237	chr2:179429966;179429965;179429964
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-139
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1095
• 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
L/H	None	None	0.997	N	0.804	0.645	0.871386344034	gnomAD-4.0.0	1.59166E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85881E-06	0	0
L/V	rs1186366124	-0.89	0.006	N	0.183	0.123	0.52586976336	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/V	rs1186366124	-0.89	0.006	N	0.183	0.123	0.52586976336	gnomAD-4.0.0	1.59165E-06	None	None	None	None	N	None	0	2.28697E-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
L/A	0.7033	likely_pathogenic	0.6852	pathogenic	-2.435	Highly Destabilizing	0.559	D	0.639	neutral	None	None	None	None	N
L/C	0.6192	likely_pathogenic	0.6324	pathogenic	-1.855	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	N
L/D	0.995	likely_pathogenic	0.9955	pathogenic	-2.797	Highly Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	N
L/E	0.9791	likely_pathogenic	0.9797	pathogenic	-2.466	Highly Destabilizing	0.978	D	0.827	deleterious	None	None	None	None	N
L/F	0.2034	likely_benign	0.222	benign	-1.454	Destabilizing	0.942	D	0.678	prob.neutral	N	0.459121933	None	None	N
L/G	0.947	likely_pathogenic	0.9455	pathogenic	-3.076	Highly Destabilizing	0.978	D	0.817	deleterious	None	None	None	None	N
L/H	0.8977	likely_pathogenic	0.914	pathogenic	-2.845	Highly Destabilizing	0.997	D	0.804	deleterious	N	0.501008628	None	None	N
L/I	0.0619	likely_benign	0.061	benign	-0.52	Destabilizing	0.006	N	0.178	neutral	N	0.36776921	None	None	N
L/K	0.9696	likely_pathogenic	0.9699	pathogenic	-1.665	Destabilizing	0.978	D	0.781	deleterious	None	None	None	None	N
L/M	0.1589	likely_benign	0.1545	benign	-0.783	Destabilizing	0.956	D	0.683	prob.neutral	None	None	None	None	N
L/N	0.9658	likely_pathogenic	0.9653	pathogenic	-2.321	Highly Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	N
L/P	0.9773	likely_pathogenic	0.9761	pathogenic	-1.146	Destabilizing	0.99	D	0.829	deleterious	N	0.507323119	None	None	N
L/Q	0.9122	likely_pathogenic	0.9182	pathogenic	-1.939	Destabilizing	0.993	D	0.787	deleterious	None	None	None	None	N
L/R	0.9332	likely_pathogenic	0.9402	pathogenic	-1.856	Destabilizing	0.97	D	0.778	deleterious	N	0.50706963	None	None	N
L/S	0.9143	likely_pathogenic	0.9154	pathogenic	-3.002	Highly Destabilizing	0.978	D	0.768	deleterious	None	None	None	None	N
L/T	0.7302	likely_pathogenic	0.7155	pathogenic	-2.487	Highly Destabilizing	0.86	D	0.712	prob.delet.	None	None	None	None	N
L/V	0.0811	likely_benign	0.0811	benign	-1.146	Destabilizing	0.006	N	0.183	neutral	N	0.416925807	None	None	N
L/W	0.7511	likely_pathogenic	0.7879	pathogenic	-1.824	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
L/Y	0.7869	likely_pathogenic	0.8001	pathogenic	-1.559	Destabilizing	0.978	D	0.781	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.