ClinVar Miner

Submissions for variant NM_198586.3(NHLRC1):c.551A>G (p.Asn184Ser) (rs138667242)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188199 SCV000241806 uncertain significance not provided 2016-03-11 criteria provided, single submitter clinical testing The N184S variant has not been published as a pathogenic variant to our knowledge. The N184S variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project or in the 1000 Genomes Project. The N184S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000691614 SCV000819400 uncertain significance Lafora disease 2018-03-19 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 184 of the NHLRC1 protein (p.Asn184Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs138667242, ExAC 0.1%). This variant has not been reported in the literature in individuals with NHLRC1-related disease. ClinVar contains an entry for this variant (Variation ID: 206178). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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