TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25154	75685;75686;75687	chr2:178570672;178570671;178570670	chr2:179435399;179435398;179435397
N2AB	23513	70762;70763;70764	chr2:178570672;178570671;178570670	chr2:179435399;179435398;179435397
N2A	22586	67981;67982;67983	chr2:178570672;178570671;178570670	chr2:179435399;179435398;179435397
N2B	16089	48490;48491;48492	chr2:178570672;178570671;178570670	chr2:179435399;179435398;179435397
Novex-1	16214	48865;48866;48867	chr2:178570672;178570671;178570670	chr2:179435399;179435398;179435397
Novex-2	16281	49066;49067;49068	chr2:178570672;178570671;178570670	chr2:179435399;179435398;179435397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-134
• Domain position: 44
• Structural Position: 70
• Q(SASA): 0.6074
• 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
N/D	None	None	None	N	0.115	0.092	0.209622950755	gnomAD-4.0.0	1.59197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85959E-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
N/A	0.1289	likely_benign	0.1373	benign	-0.355	Destabilizing	0.016	N	0.288	neutral	None	None	None	None	N
N/C	0.1733	likely_benign	0.2064	benign	0.32	Stabilizing	0.676	D	0.322	neutral	None	None	None	None	N
N/D	0.0946	likely_benign	0.0939	benign	0.251	Stabilizing	None	N	0.115	neutral	N	0.476011396	None	None	N
N/E	0.2069	likely_benign	0.2196	benign	0.213	Stabilizing	None	N	0.116	neutral	None	None	None	None	N
N/F	0.4079	ambiguous	0.4522	ambiguous	-0.756	Destabilizing	0.356	N	0.341	neutral	None	None	None	None	N
N/G	0.161	likely_benign	0.1654	benign	-0.518	Destabilizing	0.016	N	0.207	neutral	None	None	None	None	N
N/H	0.0963	likely_benign	0.1031	benign	-0.556	Destabilizing	0.295	N	0.281	neutral	D	0.530749958	None	None	N
N/I	0.1781	likely_benign	0.1942	benign	-0.015	Destabilizing	0.171	N	0.373	neutral	D	0.530576599	None	None	N
N/K	0.1848	likely_benign	0.2071	benign	0.168	Stabilizing	None	N	0.147	neutral	N	0.477472833	None	None	N
N/L	0.1599	likely_benign	0.1749	benign	-0.015	Destabilizing	0.072	N	0.357	neutral	None	None	None	None	N
N/M	0.2559	likely_benign	0.2792	benign	0.311	Stabilizing	0.628	D	0.319	neutral	None	None	None	None	N
N/P	0.2049	likely_benign	0.2163	benign	-0.102	Destabilizing	0.072	N	0.357	neutral	None	None	None	None	N
N/Q	0.217	likely_benign	0.2285	benign	-0.306	Destabilizing	0.072	N	0.153	neutral	None	None	None	None	N
N/R	0.2104	likely_benign	0.2464	benign	0.193	Stabilizing	0.038	N	0.154	neutral	None	None	None	None	N
N/S	0.0681	likely_benign	0.0682	benign	-0.099	Destabilizing	None	N	0.131	neutral	N	0.442184037	None	None	N
N/T	0.0983	likely_benign	0.1049	benign	0.01	Stabilizing	0.012	N	0.166	neutral	N	0.497482746	None	None	N
N/V	0.1574	likely_benign	0.173	benign	-0.102	Destabilizing	0.072	N	0.393	neutral	None	None	None	None	N
N/W	0.6449	likely_pathogenic	0.6972	pathogenic	-0.738	Destabilizing	0.864	D	0.367	neutral	None	None	None	None	N
N/Y	0.1387	likely_benign	0.1629	benign	-0.465	Destabilizing	0.295	N	0.333	neutral	N	0.488859562	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.