ClinVar Miner

Submissions for variant NM_002294.3(LAMP2):c.520C>A (p.Gln174Lys)

gnomAD frequency: 0.00001  dbSNP: rs104894857
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001061307 SCV001226045 uncertain significance Danon disease 2024-08-03 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 174 of the LAMP2 protein (p.Gln174Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 855949). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LAMP2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001772282 SCV001994439 uncertain significance not provided 2019-08-26 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003380830 SCV004097154 uncertain significance Cardiovascular phenotype 2023-07-13 criteria provided, single submitter clinical testing The p.Q174K variant (also known as c.520C>A), located in coding exon 4 of the LAMP2 gene, results from a C to A substitution at nucleotide position 520. The glutamine at codon 174 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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