ClinVar Miner

Submissions for variant NM_198586.3(NHLRC1):c.1090T>A (p.Ser364Thr) (rs370044232)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188202 SCV000241809 uncertain significance not provided 2016-10-21 criteria provided, single submitter clinical testing The S364T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The S364T 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 RCV000457122 SCV000551866 uncertain significance Lafora disease 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 364 of the NHLRC1 protein (p.Ser364Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is present in population databases (rs370044232, ExAC 0.007%) but has not been reported in the literature in individuals with a NHLRC1-related disease. ClinVar contains an entry for this variant (Variation ID: 206181). 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 threonine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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