TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8784	26575;26576;26577	chr2:178714424;178714423;178714422	chr2:179579151;179579150;179579149
N2AB	8467	25624;25625;25626	chr2:178714424;178714423;178714422	chr2:179579151;179579150;179579149
N2A	7540	22843;22844;22845	chr2:178714424;178714423;178714422	chr2:179579151;179579150;179579149
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-73
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.7364
• 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
W/R	rs375067750	-0.1	0.005	N	0.323	0.243	0.427254322456	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	1.66113E-04
W/R	rs375067750	-0.1	0.005	N	0.323	0.243	0.427254322456	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
W/R	rs375067750	-0.1	0.005	N	0.323	0.243	0.427254322456	gnomAD-4.0.0	1.30137E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.78001E-05	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
W/A	0.1382	likely_benign	0.1433	benign	-1.606	Destabilizing	0.304	N	0.339	neutral	None	None	None	None	N
W/C	0.3565	ambiguous	0.4178	ambiguous	-0.282	Destabilizing	0.992	D	0.293	neutral	N	0.492538286	None	None	N
W/D	0.3204	likely_benign	0.325	benign	0.637	Stabilizing	0.679	D	0.379	neutral	None	None	None	None	N
W/E	0.2441	likely_benign	0.2742	benign	0.69	Stabilizing	0.466	N	0.377	neutral	None	None	None	None	N
W/F	0.1267	likely_benign	0.1236	benign	-0.857	Destabilizing	0.932	D	0.368	neutral	None	None	None	None	N
W/G	0.1147	likely_benign	0.1156	benign	-1.792	Destabilizing	0.248	N	0.388	neutral	N	0.492018211	None	None	N
W/H	0.178	likely_benign	0.1815	benign	-0.321	Destabilizing	0.979	D	0.304	neutral	None	None	None	None	N
W/I	0.1827	likely_benign	0.1958	benign	-1.024	Destabilizing	0.938	D	0.335	neutral	None	None	None	None	N
W/K	0.1793	likely_benign	0.1978	benign	-0.288	Destabilizing	0.012	N	0.295	neutral	None	None	None	None	N
W/L	0.117	likely_benign	0.1272	benign	-1.024	Destabilizing	0.397	N	0.379	neutral	N	0.457385563	None	None	N
W/M	0.2185	likely_benign	0.2291	benign	-0.677	Destabilizing	0.979	D	0.325	neutral	None	None	None	None	N
W/N	0.2745	likely_benign	0.2609	benign	-0.509	Destabilizing	0.679	D	0.381	neutral	None	None	None	None	N
W/P	0.8375	likely_pathogenic	0.8839	pathogenic	-1.217	Destabilizing	0.938	D	0.363	neutral	None	None	None	None	N
W/Q	0.1753	likely_benign	0.2036	benign	-0.427	Destabilizing	0.679	D	0.407	neutral	None	None	None	None	N
W/R	0.1403	likely_benign	0.1619	benign	0.034	Stabilizing	0.005	N	0.323	neutral	N	0.384791959	None	None	N
W/S	0.1025	likely_benign	0.0984	benign	-1.075	Destabilizing	0.009	N	0.297	neutral	N	0.40543659	None	None	N
W/T	0.1212	likely_benign	0.12	benign	-0.977	Destabilizing	0.304	N	0.383	neutral	None	None	None	None	N
W/V	0.1587	likely_benign	0.1641	benign	-1.217	Destabilizing	0.679	D	0.377	neutral	None	None	None	None	N
W/Y	0.2064	likely_benign	0.2145	benign	-0.878	Destabilizing	0.797	D	0.349	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.