TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6797	20614;20615;20616	chr2:178725933;178725932;178725931	chr2:179590660;179590659;179590658
N2AB	6480	19663;19664;19665	chr2:178725933;178725932;178725931	chr2:179590660;179590659;179590658
N2A	5553	16882;16883;16884	chr2:178725933;178725932;178725931	chr2:179590660;179590659;179590658
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-52
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.6604
• 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
D/E	rs755018617	-0.049	0.026	D	0.251	0.247	0.104622674875	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
D/E	rs755018617	-0.049	0.026	D	0.251	0.247	0.104622674875	gnomAD-4.0.0	3.18613E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72243E-06	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
D/A	0.6779	likely_pathogenic	0.5679	pathogenic	-0.087	Destabilizing	0.19	N	0.385	neutral	D	0.575024977	None	None	N
D/C	0.9402	likely_pathogenic	0.9214	pathogenic	0.009	Stabilizing	0.998	D	0.641	neutral	None	None	None	None	N
D/E	0.3904	ambiguous	0.28	benign	-0.208	Destabilizing	0.026	N	0.251	neutral	D	0.558454587	None	None	N
D/F	0.9436	likely_pathogenic	0.8971	pathogenic	-0.134	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
D/G	0.2833	likely_benign	0.2601	benign	-0.25	Destabilizing	0.927	D	0.505	neutral	D	0.542421921	None	None	N
D/H	0.839	likely_pathogenic	0.7828	pathogenic	0.169	Stabilizing	0.998	D	0.446	neutral	D	0.595626911	None	None	N
D/I	0.9501	likely_pathogenic	0.8928	pathogenic	0.282	Stabilizing	0.998	D	0.602	neutral	None	None	None	None	N
D/K	0.9051	likely_pathogenic	0.8616	pathogenic	0.322	Stabilizing	0.988	D	0.468	neutral	None	None	None	None	N
D/L	0.8964	likely_pathogenic	0.8255	pathogenic	0.282	Stabilizing	0.997	D	0.559	neutral	None	None	None	None	N
D/M	0.962	likely_pathogenic	0.926	pathogenic	0.242	Stabilizing	1.0	D	0.612	neutral	None	None	None	None	N
D/N	0.2439	likely_benign	0.1978	benign	0.177	Stabilizing	0.195	N	0.213	neutral	N	0.510630976	None	None	N
D/P	0.9924	likely_pathogenic	0.9859	pathogenic	0.18	Stabilizing	0.921	D	0.439	neutral	None	None	None	None	N
D/Q	0.8326	likely_pathogenic	0.7559	pathogenic	0.186	Stabilizing	0.991	D	0.383	neutral	None	None	None	None	N
D/R	0.9121	likely_pathogenic	0.8773	pathogenic	0.515	Stabilizing	0.997	D	0.55	neutral	None	None	None	None	N
D/S	0.5039	ambiguous	0.4103	ambiguous	0.041	Stabilizing	0.921	D	0.449	neutral	None	None	None	None	N
D/T	0.8805	likely_pathogenic	0.7917	pathogenic	0.161	Stabilizing	0.912	D	0.464	neutral	None	None	None	None	N
D/V	0.8421	likely_pathogenic	0.7307	pathogenic	0.18	Stabilizing	0.975	D	0.559	neutral	D	0.568897615	None	None	N
D/W	0.9865	likely_pathogenic	0.978	pathogenic	-0.07	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
D/Y	0.6718	likely_pathogenic	0.578	pathogenic	0.089	Stabilizing	0.999	D	0.602	neutral	D	0.595828715	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.