ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.544A>G (p.Met182Val)

dbSNP: rs730880465
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000157924 SCV000207859 uncertain significance not provided 2013-07-15 criteria provided, single submitter clinical testing The M182V missense change has not been previously reported as a disease-causing mutation or as a benign polymorphism, to our knowledge. The amino acid substitution is conservative as both Methionine and Valine are uncharged, non-polar amino acid residues. This change occurs at a position in the C-terminal region of the protein where Methionine, Valine and other uncharged, non-polar amino acid residues are present in other species. The vast majority of missense changes in HRAS are pathogenic; however, no other missense mutations at nearby codons have been reported. In addition, in-silico algorithms are not consistent in their predictions of whether M182V is damaging to the structure/function of the protein. Therefore, based on the currently available information, it is unclear whether M182V is a disease-causing mutation or a rare benign variant.This variant has been observed to be maternally inherited. The variant is found in NOONAN panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001219043 SCV001390963 uncertain significance Costello syndrome 2024-05-22 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 182 of the HRAS protein (p.Met182Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 180853). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt HRAS function with a negative predictive value of 95%. 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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