TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6058	18397;18398;18399	chr2:178730228;178730227;178730226	chr2:179594955;179594954;179594953
N2AB	5741	17446;17447;17448	chr2:178730228;178730227;178730226	chr2:179594955;179594954;179594953
N2A	4814	14665;14666;14667	chr2:178730228;178730227;178730226	chr2:179594955;179594954;179594953
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: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-44
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2356
• 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
R/C	rs189127014	-1.729	0.079	N	0.367	0.273	None	gnomAD-2.1.1	1.71635E-04	None	None	None	None	N	None	1.48908E-03	1.41812E-04	None	0	1.54512E-04	None	3.27E-05	None	0	2.35E-05	0
R/C	rs189127014	-1.729	0.079	N	0.367	0.273	None	gnomAD-3.1.2	4.73653E-04	None	None	None	None	N	None	1.4978E-03	3.93546E-04	0	0	1.93498E-04	None	0	0	0	2.07727E-04	9.56023E-04
R/C	rs189127014	-1.729	0.079	N	0.367	0.273	None	gnomAD-4.0.0	9.91744E-05	None	None	None	None	N	None	1.57384E-03	2.50292E-04	None	0	8.93296E-05	None	0	1.65071E-04	5.08639E-06	3.29533E-05	2.08167E-04
R/H	rs376012117	-2.305	0.169	N	0.262	0.193	0.21737058555	gnomAD-2.1.1	6.08E-05	None	None	None	None	N	None	0	0	None	0	5.15E-05	None	0	None	5.20208E-04	2.35E-05	0
R/H	rs376012117	-2.305	0.169	N	0.262	0.193	0.21737058555	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	3.77216E-04	0	1.47E-05	0	0
R/H	rs376012117	-2.305	0.169	N	0.262	0.193	0.21737058555	gnomAD-4.0.0	3.59504E-05	None	None	None	None	N	None	1.33337E-05	1.66828E-05	None	0	4.46588E-05	None	4.84587E-04	0	1.61071E-05	1.09842E-05	4.80415E-05
R/L	rs376012117	-0.754	0.967	N	0.541	0.301	0.602001837285	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.9E-06	0
R/L	rs376012117	-0.754	0.967	N	0.541	0.301	0.602001837285	gnomAD-4.0.0	2.05315E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79918E-06	1.15988E-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
R/A	0.4147	ambiguous	0.465	ambiguous	-1.818	Destabilizing	0.863	D	0.422	neutral	None	None	None	None	N
R/C	0.1121	likely_benign	0.1157	benign	-1.741	Destabilizing	0.079	N	0.367	neutral	N	0.466410478	None	None	N
R/D	0.777	likely_pathogenic	0.8232	pathogenic	-0.423	Destabilizing	0.969	D	0.567	neutral	None	None	None	None	N
R/E	0.4813	ambiguous	0.5573	ambiguous	-0.217	Destabilizing	0.939	D	0.457	neutral	None	None	None	None	N
R/F	0.341	ambiguous	0.4093	ambiguous	-1.231	Destabilizing	0.991	D	0.595	neutral	None	None	None	None	N
R/G	0.3025	likely_benign	0.3527	ambiguous	-2.186	Highly Destabilizing	0.983	D	0.537	neutral	N	0.482387874	None	None	N
R/H	0.1114	likely_benign	0.1122	benign	-2.043	Highly Destabilizing	0.169	N	0.262	neutral	N	0.506120872	None	None	N
R/I	0.1884	likely_benign	0.2174	benign	-0.768	Destabilizing	0.991	D	0.593	neutral	None	None	None	None	N
R/K	0.1617	likely_benign	0.1613	benign	-1.225	Destabilizing	0.927	D	0.484	neutral	None	None	None	None	N
R/L	0.1836	likely_benign	0.2157	benign	-0.768	Destabilizing	0.967	D	0.541	neutral	N	0.515065642	None	None	N
R/M	0.269	likely_benign	0.3006	benign	-1.171	Destabilizing	0.997	D	0.513	neutral	None	None	None	None	N
R/N	0.5832	likely_pathogenic	0.6544	pathogenic	-1.037	Destabilizing	0.939	D	0.477	neutral	None	None	None	None	N
R/P	0.8058	likely_pathogenic	0.8436	pathogenic	-1.104	Destabilizing	0.998	D	0.582	neutral	N	0.494669232	None	None	N
R/Q	0.1189	likely_benign	0.1293	benign	-1.06	Destabilizing	0.991	D	0.489	neutral	None	None	None	None	N
R/S	0.4859	ambiguous	0.5345	ambiguous	-2.105	Highly Destabilizing	0.983	D	0.522	neutral	N	0.490123328	None	None	N
R/T	0.2553	likely_benign	0.2885	benign	-1.668	Destabilizing	0.969	D	0.493	neutral	None	None	None	None	N
R/V	0.2409	likely_benign	0.2689	benign	-1.104	Destabilizing	0.939	D	0.569	neutral	None	None	None	None	N
R/W	0.1199	likely_benign	0.136	benign	-0.642	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	N
R/Y	0.2082	likely_benign	0.2558	benign	-0.501	Destabilizing	0.982	D	0.575	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.