TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25494	76705;76706;76707	chr2:178569652;178569651;178569650	chr2:179434379;179434378;179434377
N2AB	23853	71782;71783;71784	chr2:178569652;178569651;178569650	chr2:179434379;179434378;179434377
N2A	22926	69001;69002;69003	chr2:178569652;178569651;178569650	chr2:179434379;179434378;179434377
N2B	16429	49510;49511;49512	chr2:178569652;178569651;178569650	chr2:179434379;179434378;179434377
Novex-1	16554	49885;49886;49887	chr2:178569652;178569651;178569650	chr2:179434379;179434378;179434377
Novex-2	16621	50086;50087;50088	chr2:178569652;178569651;178569650	chr2:179434379;179434378;179434377
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: Fn3-73
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.424
• 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	rs370908118	-0.417	0.964	N	0.741	0.146	0.202949470691	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	5.72E-05	None	0	None	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
D/A	0.1319	likely_benign	0.1252	benign	-0.218	Destabilizing	0.974	D	0.763	deleterious	N	0.462171654	None	None	N
D/C	0.486	ambiguous	0.4963	ambiguous	-0.214	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
D/E	0.149	likely_benign	0.1526	benign	-0.469	Destabilizing	0.964	D	0.741	deleterious	N	0.421148964	None	None	N
D/F	0.4483	ambiguous	0.4524	ambiguous	0.39	Stabilizing	0.99	D	0.859	deleterious	None	None	None	None	N
D/G	0.2225	likely_benign	0.2182	benign	-0.557	Destabilizing	0.914	D	0.795	deleterious	N	0.48539523	None	None	N
D/H	0.2475	likely_benign	0.2461	benign	0.36	Stabilizing	0.149	N	0.547	neutral	N	0.458249782	None	None	N
D/I	0.2152	likely_benign	0.2275	benign	0.669	Stabilizing	0.99	D	0.84	deleterious	None	None	None	None	N
D/K	0.3295	likely_benign	0.3471	ambiguous	-0.079	Destabilizing	0.98	D	0.763	deleterious	None	None	None	None	N
D/L	0.2555	likely_benign	0.2569	benign	0.669	Stabilizing	0.98	D	0.754	deleterious	None	None	None	None	N
D/M	0.4173	ambiguous	0.4337	ambiguous	0.764	Stabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
D/N	0.0852	likely_benign	0.0851	benign	-0.654	Destabilizing	0.914	D	0.851	deleterious	N	0.45308154	None	None	N
D/P	0.5443	ambiguous	0.5917	pathogenic	0.399	Stabilizing	0.997	D	0.761	deleterious	None	None	None	None	N
D/Q	0.3122	likely_benign	0.3153	benign	-0.497	Destabilizing	0.98	D	0.822	deleterious	None	None	None	None	N
D/R	0.3914	ambiguous	0.3939	ambiguous	0.242	Stabilizing	0.98	D	0.755	deleterious	None	None	None	None	N
D/S	0.1076	likely_benign	0.1067	benign	-0.839	Destabilizing	0.933	D	0.832	deleterious	None	None	None	None	N
D/T	0.1748	likely_benign	0.183	benign	-0.554	Destabilizing	0.99	D	0.773	deleterious	None	None	None	None	N
D/V	0.1281	likely_benign	0.1305	benign	0.399	Stabilizing	0.987	D	0.747	deleterious	N	0.514640702	None	None	N
D/W	0.8465	likely_pathogenic	0.8487	pathogenic	0.598	Stabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
D/Y	0.1858	likely_benign	0.1927	benign	0.651	Stabilizing	0.949	D	0.82	deleterious	N	0.461212296	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.