TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3882	11869;11870;11871	chr2:178741589;178741588;178741587	chr2:179606316;179606315;179606314
N2AB	3565	10918;10919;10920	chr2:178741589;178741588;178741587	chr2:179606316;179606315;179606314
N2A	None	None	chr2:None	chr2:None
N2B	3519	10780;10781;10782	chr2:178741589;178741588;178741587	chr2:179606316;179606315;179606314
Novex-1	3644	11155;11156;11157	chr2:178741589;178741588;178741587	chr2:179606316;179606315;179606314
Novex-2	3711	11356;11357;11358	chr2:178741589;178741588;178741587	chr2:179606316;179606315;179606314
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-27
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.5027
• 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
T/A	rs2082491063	None	None	N	0.088	0.093	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs2082491063	None	None	N	0.088	0.093	None	gnomAD-4.0.0	6.57333E-06	None	None	None	None	I	None	2.41383E-05	0	None	0	0	None	0	0	0	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
T/A	0.1071	likely_benign	0.1036	benign	-1.067	Destabilizing	None	N	0.088	neutral	N	0.422383577	None	None	I
T/C	0.4521	ambiguous	0.4081	ambiguous	-1.123	Destabilizing	0.356	N	0.417	neutral	None	None	None	None	I
T/D	0.9025	likely_pathogenic	0.8721	pathogenic	-1.983	Destabilizing	0.072	N	0.399	neutral	None	None	None	None	I
T/E	0.8235	likely_pathogenic	0.7771	pathogenic	-1.821	Destabilizing	0.072	N	0.332	neutral	None	None	None	None	I
T/F	0.8468	likely_pathogenic	0.7743	pathogenic	-0.821	Destabilizing	0.214	N	0.468	neutral	None	None	None	None	I
T/G	0.4774	ambiguous	0.4641	ambiguous	-1.435	Destabilizing	0.016	N	0.27	neutral	None	None	None	None	I
T/H	0.7683	likely_pathogenic	0.7284	pathogenic	-1.605	Destabilizing	0.628	D	0.423	neutral	None	None	None	None	I
T/I	0.5503	ambiguous	0.4831	ambiguous	-0.123	Destabilizing	0.012	N	0.325	neutral	N	0.455035704	None	None	I
T/K	0.7565	likely_pathogenic	0.6942	pathogenic	-0.794	Destabilizing	0.072	N	0.335	neutral	None	None	None	None	I
T/L	0.2699	likely_benign	0.2428	benign	-0.123	Destabilizing	0.016	N	0.269	neutral	None	None	None	None	I
T/M	0.2337	likely_benign	0.1992	benign	-0.11	Destabilizing	0.356	N	0.41	neutral	None	None	None	None	I
T/N	0.4709	ambiguous	0.4424	ambiguous	-1.468	Destabilizing	0.055	N	0.412	neutral	N	0.508872947	None	None	I
T/P	0.1976	likely_benign	0.1919	benign	-0.406	Destabilizing	0.055	N	0.476	neutral	N	0.506984444	None	None	I
T/Q	0.6849	likely_pathogenic	0.6359	pathogenic	-1.371	Destabilizing	0.356	N	0.471	neutral	None	None	None	None	I
T/R	0.6279	likely_pathogenic	0.5684	pathogenic	-0.848	Destabilizing	0.072	N	0.48	neutral	None	None	None	None	I
T/S	0.1939	likely_benign	0.1884	benign	-1.579	Destabilizing	None	N	0.103	neutral	N	0.508397071	None	None	I
T/V	0.3471	ambiguous	0.3023	benign	-0.406	Destabilizing	None	N	0.107	neutral	None	None	None	None	I
T/W	0.9557	likely_pathogenic	0.9315	pathogenic	-0.991	Destabilizing	0.864	D	0.439	neutral	None	None	None	None	I
T/Y	0.8745	likely_pathogenic	0.8165	pathogenic	-0.608	Destabilizing	0.356	N	0.433	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.