TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23292	70099;70100;70101	chr2:178576258;178576257;178576256	chr2:179440985;179440984;179440983
N2AB	21651	65176;65177;65178	chr2:178576258;178576257;178576256	chr2:179440985;179440984;179440983
N2A	20724	62395;62396;62397	chr2:178576258;178576257;178576256	chr2:179440985;179440984;179440983
N2B	14227	42904;42905;42906	chr2:178576258;178576257;178576256	chr2:179440985;179440984;179440983
Novex-1	14352	43279;43280;43281	chr2:178576258;178576257;178576256	chr2:179440985;179440984;179440983
Novex-2	14419	43480;43481;43482	chr2:178576258;178576257;178576256	chr2:179440985;179440984;179440983
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-57
• Domain position: 53
• Structural Position: 70
• Q(SASA): 1.0249
• 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/R	rs1710041063	None	0.879	N	0.407	0.343	0.330331372229	gnomAD-4.0.0	1.59613E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86428E-06	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	0.0746	likely_benign	0.0746	benign	-0.176	Destabilizing	0.296	N	0.445	neutral	N	0.484808945	None	None	I
T/C	0.4284	ambiguous	0.3994	ambiguous	-0.408	Destabilizing	0.991	D	0.455	neutral	None	None	None	None	I
T/D	0.3416	ambiguous	0.3109	benign	-0.051	Destabilizing	0.906	D	0.401	neutral	None	None	None	None	I
T/E	0.246	likely_benign	0.2232	benign	-0.145	Destabilizing	0.826	D	0.401	neutral	None	None	None	None	I
T/F	0.3288	likely_benign	0.2821	benign	-0.873	Destabilizing	0.826	D	0.512	neutral	None	None	None	None	I
T/G	0.206	likely_benign	0.1903	benign	-0.207	Destabilizing	0.826	D	0.422	neutral	None	None	None	None	I
T/H	0.2506	likely_benign	0.2261	benign	-0.366	Destabilizing	0.991	D	0.513	neutral	None	None	None	None	I
T/I	0.2149	likely_benign	0.1729	benign	-0.211	Destabilizing	0.007	N	0.311	neutral	N	0.518766803	None	None	I
T/K	0.1664	likely_benign	0.1497	benign	-0.289	Destabilizing	0.782	D	0.402	neutral	N	0.489601477	None	None	I
T/L	0.131	likely_benign	0.1116	benign	-0.211	Destabilizing	0.189	N	0.474	neutral	None	None	None	None	I
T/M	0.1185	likely_benign	0.1061	benign	-0.221	Destabilizing	0.947	D	0.415	neutral	None	None	None	None	I
T/N	0.1391	likely_benign	0.1336	benign	-0.107	Destabilizing	0.906	D	0.377	neutral	None	None	None	None	I
T/P	0.1067	likely_benign	0.1029	benign	-0.178	Destabilizing	0.003	N	0.319	neutral	N	0.490929628	None	None	I
T/Q	0.1893	likely_benign	0.1747	benign	-0.298	Destabilizing	0.906	D	0.409	neutral	None	None	None	None	I
T/R	0.1565	likely_benign	0.1406	benign	-0.039	Destabilizing	0.879	D	0.407	neutral	N	0.494737937	None	None	I
T/S	0.0992	likely_benign	0.1	benign	-0.261	Destabilizing	0.505	D	0.455	neutral	N	0.483502223	None	None	I
T/V	0.1506	likely_benign	0.1275	benign	-0.178	Destabilizing	0.189	N	0.445	neutral	None	None	None	None	I
T/W	0.6262	likely_pathogenic	0.5861	pathogenic	-0.974	Destabilizing	0.991	D	0.623	neutral	None	None	None	None	I
T/Y	0.3413	ambiguous	0.3183	benign	-0.651	Destabilizing	0.906	D	0.509	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.