TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17710	53353;53354;53355	chr2:178607560;178607559;178607558	chr2:179472287;179472286;179472285
N2AB	16069	48430;48431;48432	chr2:178607560;178607559;178607558	chr2:179472287;179472286;179472285
N2A	15142	45649;45650;45651	chr2:178607560;178607559;178607558	chr2:179472287;179472286;179472285
N2B	8645	26158;26159;26160	chr2:178607560;178607559;178607558	chr2:179472287;179472286;179472285
Novex-1	8770	26533;26534;26535	chr2:178607560;178607559;178607558	chr2:179472287;179472286;179472285
Novex-2	8837	26734;26735;26736	chr2:178607560;178607559;178607558	chr2:179472287;179472286;179472285
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-113
• Domain position: 34
• Structural Position: 52
• Q(SASA): 0.9512
• 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
E/D	rs749551895	-0.084	None	N	0.135	0.104	0.0666544352282	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
E/D	rs749551895	-0.084	None	N	0.135	0.104	0.0666544352282	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs749551895	-0.084	None	N	0.135	0.104	0.0666544352282	gnomAD-4.0.0	6.57964E-06	None	None	None	None	N	None	2.41313E-05	0	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
E/A	0.1551	likely_benign	0.1738	benign	0.014	Stabilizing	0.052	N	0.397	neutral	N	0.478277257	None	None	N
E/C	0.7666	likely_pathogenic	0.8231	pathogenic	-0.126	Destabilizing	0.935	D	0.505	neutral	None	None	None	None	N
E/D	0.0829	likely_benign	0.0787	benign	-0.295	Destabilizing	None	N	0.135	neutral	N	0.422863904	None	None	N
E/F	0.7325	likely_pathogenic	0.7829	pathogenic	-0.05	Destabilizing	0.791	D	0.463	neutral	None	None	None	None	N
E/G	0.1114	likely_benign	0.1341	benign	-0.086	Destabilizing	None	N	0.284	neutral	N	0.334775199	None	None	N
E/H	0.5483	ambiguous	0.6026	pathogenic	0.511	Stabilizing	0.555	D	0.383	neutral	None	None	None	None	N
E/I	0.4364	ambiguous	0.4735	ambiguous	0.218	Stabilizing	0.555	D	0.466	neutral	None	None	None	None	N
E/K	0.2498	likely_benign	0.2863	benign	0.468	Stabilizing	0.117	N	0.443	neutral	N	0.438084073	None	None	N
E/L	0.4631	ambiguous	0.5141	ambiguous	0.218	Stabilizing	0.38	N	0.482	neutral	None	None	None	None	N
E/M	0.5095	ambiguous	0.5418	ambiguous	0.035	Stabilizing	0.935	D	0.447	neutral	None	None	None	None	N
E/N	0.2025	likely_benign	0.2126	benign	0.231	Stabilizing	0.081	N	0.403	neutral	None	None	None	None	N
E/P	0.5359	ambiguous	0.5944	pathogenic	0.167	Stabilizing	0.555	D	0.435	neutral	None	None	None	None	N
E/Q	0.2283	likely_benign	0.2455	benign	0.242	Stabilizing	0.117	N	0.438	neutral	N	0.487339457	None	None	N
E/R	0.389	ambiguous	0.4444	ambiguous	0.634	Stabilizing	0.38	N	0.416	neutral	None	None	None	None	N
E/S	0.1932	likely_benign	0.2139	benign	0.106	Stabilizing	0.081	N	0.401	neutral	None	None	None	None	N
E/T	0.2162	likely_benign	0.2288	benign	0.2	Stabilizing	0.149	N	0.433	neutral	None	None	None	None	N
E/V	0.2722	likely_benign	0.3071	benign	0.167	Stabilizing	0.484	N	0.456	neutral	N	0.512813905	None	None	N
E/W	0.8515	likely_pathogenic	0.8967	pathogenic	-0.021	Destabilizing	0.935	D	0.551	neutral	None	None	None	None	N
E/Y	0.5658	likely_pathogenic	0.6298	pathogenic	0.166	Stabilizing	0.791	D	0.45	neutral	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.