TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33722	101389;101390;101391	chr2:178535451;178535450;178535449	chr2:179400178;179400177;179400176
N2AB	32081	96466;96467;96468	chr2:178535451;178535450;178535449	chr2:179400178;179400177;179400176
N2A	31154	93685;93686;93687	chr2:178535451;178535450;178535449	chr2:179400178;179400177;179400176
N2B	24657	74194;74195;74196	chr2:178535451;178535450;178535449	chr2:179400178;179400177;179400176
Novex-1	24782	74569;74570;74571	chr2:178535451;178535450;178535449	chr2:179400178;179400177;179400176
Novex-2	24849	74770;74771;74772	chr2:178535451;178535450;178535449	chr2:179400178;179400177;179400176
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: Fn3-132
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4105
• 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
T/I	rs1372744849	None	0.017	N	0.151	0.175	0.245660935333	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1372744849	None	0.017	N	0.151	0.175	0.245660935333	gnomAD-4.0.0	2.56195E-06	None	None	None	None	N	None	1.69142E-05	0	None	0	0	None	0	0	0	0	2.84398E-05
T/S	None	None	0.646	N	0.459	0.302	0.219573609325	gnomAD-4.0.0	3.18234E-06	None	None	None	None	N	None	0	4.57373E-05	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	0.1489	likely_benign	0.1748	benign	-0.744	Destabilizing	0.271	N	0.431	neutral	N	0.499680937	None	None	N
T/C	0.5342	ambiguous	0.5969	pathogenic	-0.481	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
T/D	0.6268	likely_pathogenic	0.6922	pathogenic	-0.408	Destabilizing	0.988	D	0.503	neutral	None	None	None	None	N
T/E	0.4277	ambiguous	0.5058	ambiguous	-0.424	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	N
T/F	0.4144	ambiguous	0.4638	ambiguous	-0.85	Destabilizing	0.994	D	0.596	neutral	None	None	None	None	N
T/G	0.4278	ambiguous	0.4555	ambiguous	-0.986	Destabilizing	0.999	D	0.493	neutral	None	None	None	None	N
T/H	0.4003	ambiguous	0.4537	ambiguous	-1.314	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
T/I	0.1462	likely_benign	0.2032	benign	-0.196	Destabilizing	0.017	N	0.151	neutral	N	0.488700186	None	None	N
T/K	0.2893	likely_benign	0.3459	ambiguous	-0.818	Destabilizing	0.992	D	0.501	neutral	None	None	None	None	N
T/L	0.1241	likely_benign	0.1571	benign	-0.196	Destabilizing	0.779	D	0.417	neutral	None	None	None	None	N
T/M	0.1244	likely_benign	0.1515	benign	0.153	Stabilizing	0.984	D	0.558	neutral	None	None	None	None	N
T/N	0.1943	likely_benign	0.2318	benign	-0.71	Destabilizing	0.984	D	0.511	neutral	N	0.491794125	None	None	N
T/P	0.6368	likely_pathogenic	0.693	pathogenic	-0.347	Destabilizing	0.984	D	0.553	neutral	N	0.519559619	None	None	N
T/Q	0.2909	likely_benign	0.3432	ambiguous	-0.927	Destabilizing	0.994	D	0.555	neutral	None	None	None	None	N
T/R	0.2319	likely_benign	0.2661	benign	-0.542	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
T/S	0.1834	likely_benign	0.1978	benign	-0.948	Destabilizing	0.646	D	0.459	neutral	N	0.519983099	None	None	N
T/V	0.1473	likely_benign	0.1883	benign	-0.347	Destabilizing	0.525	D	0.325	neutral	None	None	None	None	N
T/W	0.7592	likely_pathogenic	0.807	pathogenic	-0.785	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
T/Y	0.4895	ambiguous	0.5708	pathogenic	-0.562	Destabilizing	0.999	D	0.608	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.