TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35752	107479;107480;107481	chr2:178528397;178528396;178528395	chr2:179393124;179393123;179393122
N2AB	34111	102556;102557;102558	chr2:178528397;178528396;178528395	chr2:179393124;179393123;179393122
N2A	33184	99775;99776;99777	chr2:178528397;178528396;178528395	chr2:179393124;179393123;179393122
N2B	26687	80284;80285;80286	chr2:178528397;178528396;178528395	chr2:179393124;179393123;179393122
Novex-1	26812	80659;80660;80661	chr2:178528397;178528396;178528395	chr2:179393124;179393123;179393122
Novex-2	26879	80860;80861;80862	chr2:178528397;178528396;178528395	chr2:179393124;179393123;179393122
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-168
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.7121
• Predicted PPI site: I

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	rs528535076	-0.433	0.487	N	0.515	0.331	0.554196100949	gnomAD-2.1.1	2.25162E-04	None	None	None	None	I	None	6.46E-05	0	None	0	5.57E-05	None	1.73566E-03	None	0	0	1.65728E-04
R/C	rs528535076	-0.433	0.487	N	0.515	0.331	0.554196100949	gnomAD-3.1.2	3.94E-05	None	None	None	None	I	None	0	0	0	0	1.92308E-04	None	0	0	1.47E-05	8.27815E-04	0
R/C	rs528535076	-0.433	0.487	N	0.515	0.331	0.554196100949	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/C	rs528535076	-0.433	0.487	N	0.515	0.331	0.554196100949	gnomAD-4.0.0	9.91492E-05	None	None	None	None	I	None	2.66596E-05	0	None	0	2.22806E-05	None	0	0	2.5428E-06	1.6045E-03	1.28037E-04
R/H	rs760107623	-1.194	0.999	N	0.529	0.301	0.284150004643	gnomAD-2.1.1	4.83E-05	None	None	None	None	I	None	0	2.9E-05	None	0	2.78396E-04	None	9.83E-05	None	4.64E-05	1.78E-05	0
R/H	rs760107623	-1.194	0.999	N	0.529	0.301	0.284150004643	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	3.84468E-04	None	0	0	1.47E-05	0	0
R/H	rs760107623	-1.194	0.999	N	0.529	0.301	0.284150004643	gnomAD-4.0.0	2.78894E-05	None	None	None	None	I	None	1.3354E-05	1.66861E-05	None	0	2.00463E-04	None	3.1252E-05	0	2.03425E-05	8.7943E-05	0
R/L	None	None	0.983	N	0.588	0.292	0.565131857978	gnomAD-4.0.0	1.36855E-06	None	None	None	None	I	None	2.98811E-05	0	None	0	0	None	0	0	0	1.16082E-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	0.5388	ambiguous	0.5169	ambiguous	-0.33	Destabilizing	0.927	D	0.533	neutral	None	None	None	None	I
R/C	0.2784	likely_benign	0.3056	benign	-0.475	Destabilizing	0.487	N	0.515	neutral	N	0.50471815	None	None	I
R/D	0.8176	likely_pathogenic	0.7932	pathogenic	0.033	Stabilizing	0.991	D	0.534	neutral	None	None	None	None	I
R/E	0.4736	ambiguous	0.4467	ambiguous	0.118	Stabilizing	0.939	D	0.492	neutral	None	None	None	None	I
R/F	0.6971	likely_pathogenic	0.6995	pathogenic	-0.532	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	I
R/G	0.371	ambiguous	0.3449	ambiguous	-0.543	Destabilizing	0.992	D	0.581	neutral	N	0.4788597	None	None	I
R/H	0.1263	likely_benign	0.135	benign	-1.072	Destabilizing	0.999	D	0.529	neutral	N	0.47680083	None	None	I
R/I	0.4391	ambiguous	0.4199	ambiguous	0.206	Stabilizing	0.991	D	0.541	neutral	None	None	None	None	I
R/K	0.1384	likely_benign	0.1361	benign	-0.281	Destabilizing	0.864	D	0.463	neutral	None	None	None	None	I
R/L	0.408	ambiguous	0.4108	ambiguous	0.206	Stabilizing	0.983	D	0.588	neutral	N	0.472952448	None	None	I
R/M	0.4993	ambiguous	0.4907	ambiguous	-0.21	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	I
R/N	0.7004	likely_pathogenic	0.676	pathogenic	-0.057	Destabilizing	0.984	D	0.513	neutral	None	None	None	None	I
R/P	0.7929	likely_pathogenic	0.7775	pathogenic	0.048	Stabilizing	0.999	D	0.555	neutral	N	0.461890092	None	None	I
R/Q	0.1225	likely_benign	0.1259	benign	-0.155	Destabilizing	0.736	D	0.291	neutral	None	None	None	None	I
R/S	0.5594	ambiguous	0.5426	ambiguous	-0.568	Destabilizing	0.967	D	0.549	neutral	N	0.424486497	None	None	I
R/T	0.3926	ambiguous	0.3781	ambiguous	-0.328	Destabilizing	0.293	N	0.379	neutral	None	None	None	None	I
R/V	0.5397	ambiguous	0.5361	ambiguous	0.048	Stabilizing	0.969	D	0.549	neutral	None	None	None	None	I
R/W	0.278	likely_benign	0.3	benign	-0.5	Destabilizing	1.0	D	0.551	neutral	None	None	None	None	I
R/Y	0.5172	ambiguous	0.5216	ambiguous	-0.107	Destabilizing	0.999	D	0.549	neutral	None	None	None	None	I

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.