TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25144	75655;75656;75657	chr2:178570702;178570701;178570700	chr2:179435429;179435428;179435427
N2AB	23503	70732;70733;70734	chr2:178570702;178570701;178570700	chr2:179435429;179435428;179435427
N2A	22576	67951;67952;67953	chr2:178570702;178570701;178570700	chr2:179435429;179435428;179435427
N2B	16079	48460;48461;48462	chr2:178570702;178570701;178570700	chr2:179435429;179435428;179435427
Novex-1	16204	48835;48836;48837	chr2:178570702;178570701;178570700	chr2:179435429;179435428;179435427
Novex-2	16271	49036;49037;49038	chr2:178570702;178570701;178570700	chr2:179435429;179435428;179435427
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-134
• Domain position: 34
• Structural Position: 47
• Q(SASA): 0.5319
• 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
Q/L	rs1168512437	0.634	0.213	N	0.493	0.231	0.373537453441	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/L	rs1168512437	0.634	0.213	N	0.493	0.231	0.373537453441	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
Q/A	0.1867	likely_benign	0.1991	benign	-0.42	Destabilizing	0.129	N	0.434	neutral	None	None	None	None	N
Q/C	0.3439	ambiguous	0.3995	ambiguous	0.008	Stabilizing	0.983	D	0.538	neutral	None	None	None	None	N
Q/D	0.271	likely_benign	0.3088	benign	-0.147	Destabilizing	0.129	N	0.416	neutral	None	None	None	None	N
Q/E	0.0668	likely_benign	0.0688	benign	-0.075	Destabilizing	0.001	N	0.169	neutral	N	0.436471573	None	None	N
Q/F	0.463	ambiguous	0.5197	ambiguous	-0.142	Destabilizing	0.836	D	0.531	neutral	None	None	None	None	N
Q/G	0.2715	likely_benign	0.2931	benign	-0.746	Destabilizing	0.228	N	0.471	neutral	None	None	None	None	N
Q/H	0.1179	likely_benign	0.1309	benign	-0.508	Destabilizing	0.001	N	0.161	neutral	N	0.453790684	None	None	N
Q/I	0.2256	likely_benign	0.2503	benign	0.391	Stabilizing	0.716	D	0.566	neutral	None	None	None	None	N
Q/K	0.0927	likely_benign	0.0992	benign	-0.241	Destabilizing	0.101	N	0.413	neutral	N	0.467949273	None	None	N
Q/L	0.0999	likely_benign	0.1135	benign	0.391	Stabilizing	0.213	N	0.493	neutral	N	0.502101919	None	None	N
Q/M	0.2498	likely_benign	0.2734	benign	0.564	Stabilizing	0.94	D	0.479	neutral	None	None	None	None	N
Q/N	0.2168	likely_benign	0.242	benign	-0.721	Destabilizing	0.228	N	0.395	neutral	None	None	None	None	N
Q/P	0.7187	likely_pathogenic	0.7678	pathogenic	0.152	Stabilizing	0.523	D	0.533	neutral	N	0.503356192	None	None	N
Q/R	0.0978	likely_benign	0.1058	benign	-0.163	Destabilizing	0.002	N	0.181	neutral	N	0.44888351	None	None	N
Q/S	0.1654	likely_benign	0.1786	benign	-0.785	Destabilizing	0.129	N	0.417	neutral	None	None	None	None	N
Q/T	0.1195	likely_benign	0.1255	benign	-0.525	Destabilizing	0.002	N	0.273	neutral	None	None	None	None	N
Q/V	0.1552	likely_benign	0.1718	benign	0.152	Stabilizing	0.264	N	0.532	neutral	None	None	None	None	N
Q/W	0.3876	ambiguous	0.4376	ambiguous	-0.05	Destabilizing	0.983	D	0.54	neutral	None	None	None	None	N
Q/Y	0.2743	likely_benign	0.3223	benign	0.167	Stabilizing	0.418	N	0.562	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.