TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24956	75091;75092;75093	chr2:178571266;178571265;178571264	chr2:179435993;179435992;179435991
N2AB	23315	70168;70169;70170	chr2:178571266;178571265;178571264	chr2:179435993;179435992;179435991
N2A	22388	67387;67388;67389	chr2:178571266;178571265;178571264	chr2:179435993;179435992;179435991
N2B	15891	47896;47897;47898	chr2:178571266;178571265;178571264	chr2:179435993;179435992;179435991
Novex-1	16016	48271;48272;48273	chr2:178571266;178571265;178571264	chr2:179435993;179435992;179435991
Novex-2	16083	48472;48473;48474	chr2:178571266;178571265;178571264	chr2:179435993;179435992;179435991
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-69
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.384
• 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
V/I	rs375784858	-0.155	None	N	0.161	0.068	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs375784858	-0.155	None	N	0.161	0.068	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
V/A	0.1881	likely_benign	0.2384	benign	-1.017	Destabilizing	None	N	0.167	neutral	N	0.501106549	None	None	N
V/C	0.583	likely_pathogenic	0.6324	pathogenic	-0.731	Destabilizing	0.935	D	0.386	neutral	None	None	None	None	N
V/D	0.4664	ambiguous	0.5119	ambiguous	-0.62	Destabilizing	0.317	N	0.444	neutral	N	0.506917801	None	None	N
V/E	0.3309	likely_benign	0.356	ambiguous	-0.609	Destabilizing	0.38	N	0.413	neutral	None	None	None	None	N
V/F	0.1769	likely_benign	0.2081	benign	-0.644	Destabilizing	0.188	N	0.417	neutral	N	0.513459771	None	None	N
V/G	0.2053	likely_benign	0.2397	benign	-1.313	Destabilizing	0.062	N	0.372	neutral	N	0.472560553	None	None	N
V/H	0.5019	ambiguous	0.5481	ambiguous	-0.71	Destabilizing	0.935	D	0.445	neutral	None	None	None	None	N
V/I	0.0777	likely_benign	0.0792	benign	-0.315	Destabilizing	None	N	0.161	neutral	N	0.47936584	None	None	N
V/K	0.4186	ambiguous	0.4311	ambiguous	-0.888	Destabilizing	0.38	N	0.411	neutral	None	None	None	None	N
V/L	0.1545	likely_benign	0.1745	benign	-0.315	Destabilizing	None	N	0.199	neutral	N	0.495892731	None	None	N
V/M	0.1104	likely_benign	0.1193	benign	-0.38	Destabilizing	0.235	N	0.461	neutral	None	None	None	None	N
V/N	0.1916	likely_benign	0.2406	benign	-0.779	Destabilizing	0.38	N	0.459	neutral	None	None	None	None	N
V/P	0.9158	likely_pathogenic	0.9363	pathogenic	-0.514	Destabilizing	0.555	D	0.445	neutral	None	None	None	None	N
V/Q	0.2675	likely_benign	0.289	benign	-0.884	Destabilizing	0.555	D	0.421	neutral	None	None	None	None	N
V/R	0.4172	ambiguous	0.4297	ambiguous	-0.425	Destabilizing	0.555	D	0.447	neutral	None	None	None	None	N
V/S	0.1764	likely_benign	0.229	benign	-1.293	Destabilizing	0.016	N	0.309	neutral	None	None	None	None	N
V/T	0.1501	likely_benign	0.1883	benign	-1.169	Destabilizing	0.081	N	0.328	neutral	None	None	None	None	N
V/W	0.8134	likely_pathogenic	0.8262	pathogenic	-0.844	Destabilizing	0.935	D	0.55	neutral	None	None	None	None	N
V/Y	0.4745	ambiguous	0.5006	ambiguous	-0.525	Destabilizing	0.555	D	0.41	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.