TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22686	68281;68282;68283	chr2:178578974;178578973;178578972	chr2:179443701;179443700;179443699
N2AB	21045	63358;63359;63360	chr2:178578974;178578973;178578972	chr2:179443701;179443700;179443699
N2A	20118	60577;60578;60579	chr2:178578974;178578973;178578972	chr2:179443701;179443700;179443699
N2B	13621	41086;41087;41088	chr2:178578974;178578973;178578972	chr2:179443701;179443700;179443699
Novex-1	13746	41461;41462;41463	chr2:178578974;178578973;178578972	chr2:179443701;179443700;179443699
Novex-2	13813	41662;41663;41664	chr2:178578974;178578973;178578972	chr2:179443701;179443700;179443699
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-52
• Domain position: 44
• Structural Position: 50
• Q(SASA): 0.3311
• 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
S/T	None	None	0.007	N	0.137	0.049	0.0762999501168	gnomAD-4.0.0	1.59237E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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
S/A	0.0947	likely_benign	0.0861	benign	-0.715	Destabilizing	0.002	N	0.137	neutral	N	0.453718034	None	None	N
S/C	0.1258	likely_benign	0.1146	benign	-0.433	Destabilizing	0.97	D	0.412	neutral	N	0.512054262	None	None	N
S/D	0.476	ambiguous	0.4084	ambiguous	-0.599	Destabilizing	0.447	N	0.245	neutral	None	None	None	None	N
S/E	0.6503	likely_pathogenic	0.5912	pathogenic	-0.605	Destabilizing	0.617	D	0.256	neutral	None	None	None	None	N
S/F	0.3653	ambiguous	0.3241	benign	-0.881	Destabilizing	0.896	D	0.524	neutral	N	0.501146622	None	None	N
S/G	0.092	likely_benign	0.0873	benign	-0.968	Destabilizing	0.25	N	0.296	neutral	None	None	None	None	N
S/H	0.365	ambiguous	0.3176	benign	-1.503	Destabilizing	0.85	D	0.421	neutral	None	None	None	None	N
S/I	0.1723	likely_benign	0.1515	benign	-0.146	Destabilizing	0.85	D	0.497	neutral	None	None	None	None	N
S/K	0.6806	likely_pathogenic	0.6042	pathogenic	-0.896	Destabilizing	0.447	N	0.271	neutral	None	None	None	None	N
S/L	0.1524	likely_benign	0.1361	benign	-0.146	Destabilizing	0.447	N	0.451	neutral	None	None	None	None	N
S/M	0.2292	likely_benign	0.217	benign	0.225	Stabilizing	0.972	D	0.418	neutral	None	None	None	None	N
S/N	0.1273	likely_benign	0.1127	benign	-0.832	Destabilizing	0.002	N	0.137	neutral	None	None	None	None	N
S/P	0.431	ambiguous	0.3817	ambiguous	-0.301	Destabilizing	0.896	D	0.385	neutral	N	0.46947692	None	None	N
S/Q	0.5348	ambiguous	0.4946	ambiguous	-0.985	Destabilizing	0.85	D	0.369	neutral	None	None	None	None	N
S/R	0.595	likely_pathogenic	0.5232	ambiguous	-0.756	Destabilizing	0.617	D	0.386	neutral	None	None	None	None	N
S/T	0.0849	likely_benign	0.0816	benign	-0.787	Destabilizing	0.007	N	0.137	neutral	N	0.422837767	None	None	N
S/V	0.1888	likely_benign	0.1683	benign	-0.301	Destabilizing	0.447	N	0.459	neutral	None	None	None	None	N
S/W	0.5332	ambiguous	0.4887	ambiguous	-0.895	Destabilizing	0.992	D	0.568	neutral	None	None	None	None	N
S/Y	0.2978	likely_benign	0.2555	benign	-0.645	Destabilizing	0.963	D	0.522	neutral	N	0.517577512	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.