TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27746	83461;83462;83463	chr2:178562896;178562895;178562894	chr2:179427623;179427622;179427621
N2AB	26105	78538;78539;78540	chr2:178562896;178562895;178562894	chr2:179427623;179427622;179427621
N2A	25178	75757;75758;75759	chr2:178562896;178562895;178562894	chr2:179427623;179427622;179427621
N2B	18681	56266;56267;56268	chr2:178562896;178562895;178562894	chr2:179427623;179427622;179427621
Novex-1	18806	56641;56642;56643	chr2:178562896;178562895;178562894	chr2:179427623;179427622;179427621
Novex-2	18873	56842;56843;56844	chr2:178562896;178562895;178562894	chr2:179427623;179427622;179427621
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-141
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0846
• 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
L/V	rs1018294368	-1.156	0.767	N	0.401	0.128	0.300784259202	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/V	rs1018294368	-1.156	0.767	N	0.401	0.128	0.300784259202	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs1018294368	-1.156	0.767	N	0.401	0.128	0.300784259202	gnomAD-4.0.0	6.57479E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47033E-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
L/A	0.9607	likely_pathogenic	0.9586	pathogenic	-2.557	Highly Destabilizing	0.997	D	0.779	deleterious	None	None	None	None	N
L/C	0.9097	likely_pathogenic	0.9075	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-2.851	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/E	0.999	likely_pathogenic	0.999	pathogenic	-2.638	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
L/F	0.9075	likely_pathogenic	0.8826	pathogenic	-1.604	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/G	0.9963	likely_pathogenic	0.9964	pathogenic	-3.109	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/H	0.9976	likely_pathogenic	0.9976	pathogenic	-2.554	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/I	0.1832	likely_benign	0.179	benign	-0.969	Destabilizing	0.985	D	0.688	prob.neutral	None	None	None	None	N
L/K	0.9977	likely_pathogenic	0.998	pathogenic	-1.939	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/M	0.4412	ambiguous	0.4249	ambiguous	-0.972	Destabilizing	0.999	D	0.76	deleterious	N	0.466594347	None	None	N
L/N	0.9987	likely_pathogenic	0.9989	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/P	0.9991	likely_pathogenic	0.9992	pathogenic	-1.478	Destabilizing	1.0	D	0.901	deleterious	N	0.505120262	None	None	N
L/Q	0.9955	likely_pathogenic	0.9959	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.901	deleterious	N	0.505120262	None	None	N
L/R	0.9949	likely_pathogenic	0.9957	pathogenic	-1.628	Destabilizing	1.0	D	0.896	deleterious	N	0.505120262	None	None	N
L/S	0.9978	likely_pathogenic	0.9976	pathogenic	-2.995	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/T	0.9831	likely_pathogenic	0.9823	pathogenic	-2.628	Highly Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
L/V	0.191	likely_benign	0.1935	benign	-1.478	Destabilizing	0.767	D	0.401	neutral	N	0.462979731	None	None	N
L/W	0.9964	likely_pathogenic	0.996	pathogenic	-1.975	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/Y	0.9941	likely_pathogenic	0.9933	pathogenic	-1.688	Destabilizing	1.0	D	0.837	deleterious	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.