TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22823	68692;68693;68694	chr2:178578048;178578047;178578046	chr2:179442775;179442774;179442773
N2AB	21182	63769;63770;63771	chr2:178578048;178578047;178578046	chr2:179442775;179442774;179442773
N2A	20255	60988;60989;60990	chr2:178578048;178578047;178578046	chr2:179442775;179442774;179442773
N2B	13758	41497;41498;41499	chr2:178578048;178578047;178578046	chr2:179442775;179442774;179442773
Novex-1	13883	41872;41873;41874	chr2:178578048;178578047;178578046	chr2:179442775;179442774;179442773
Novex-2	13950	42073;42074;42075	chr2:178578048;178578047;178578046	chr2:179442775;179442774;179442773
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-53
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.9486
• 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
L/S	rs770040120	-0.127	0.669	N	0.573	0.334	0.628610474668	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
L/S	rs770040120	-0.127	0.669	N	0.573	0.334	0.628610474668	gnomAD-4.0.0	1.59253E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86041E-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
L/A	0.2078	likely_benign	0.1984	benign	-0.38	Destabilizing	0.067	N	0.259	neutral	None	None	None	None	I
L/C	0.6285	likely_pathogenic	0.6281	pathogenic	-0.635	Destabilizing	0.998	D	0.476	neutral	None	None	None	None	I
L/D	0.7831	likely_pathogenic	0.7948	pathogenic	-0.105	Destabilizing	0.991	D	0.591	neutral	None	None	None	None	I
L/E	0.4731	ambiguous	0.4955	ambiguous	-0.213	Destabilizing	0.974	D	0.569	neutral	None	None	None	None	I
L/F	0.2054	likely_benign	0.2082	benign	-0.583	Destabilizing	0.934	D	0.403	neutral	N	0.470608316	None	None	I
L/G	0.5771	likely_pathogenic	0.5797	pathogenic	-0.489	Destabilizing	0.842	D	0.557	neutral	None	None	None	None	I
L/H	0.2858	likely_benign	0.3114	benign	0.072	Stabilizing	0.998	D	0.581	neutral	None	None	None	None	I
L/I	0.0975	likely_benign	0.1018	benign	-0.228	Destabilizing	0.454	N	0.415	neutral	N	0.37227566	None	None	I
L/K	0.3108	likely_benign	0.3631	ambiguous	-0.181	Destabilizing	0.949	D	0.519	neutral	None	None	None	None	I
L/M	0.0944	likely_benign	0.0863	benign	-0.348	Destabilizing	0.172	N	0.308	neutral	None	None	None	None	I
L/N	0.4463	ambiguous	0.4337	ambiguous	-0.015	Destabilizing	0.991	D	0.59	neutral	None	None	None	None	I
L/P	0.5102	ambiguous	0.5837	pathogenic	-0.248	Destabilizing	0.991	D	0.597	neutral	None	None	None	None	I
L/Q	0.1769	likely_benign	0.1831	benign	-0.231	Destabilizing	0.974	D	0.588	neutral	None	None	None	None	I
L/R	0.2587	likely_benign	0.3157	benign	0.302	Stabilizing	0.974	D	0.594	neutral	None	None	None	None	I
L/S	0.3038	likely_benign	0.2913	benign	-0.411	Destabilizing	0.669	D	0.573	neutral	N	0.394323014	None	None	I
L/T	0.2285	likely_benign	0.2301	benign	-0.413	Destabilizing	0.842	D	0.546	neutral	None	None	None	None	I
L/V	0.0955	likely_benign	0.0969	benign	-0.248	Destabilizing	0.051	N	0.227	neutral	N	0.440634094	None	None	I
L/W	0.3707	ambiguous	0.4209	ambiguous	-0.611	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	I
L/Y	0.4073	ambiguous	0.4211	ambiguous	-0.341	Destabilizing	0.974	D	0.485	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.