ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.490C>T (p.Arg164Trp)

gnomAD frequency: 0.00001  dbSNP: rs779101895
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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 RCV000703060 SCV000831941 uncertain significance Costello syndrome 2023-09-17 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 579709). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. This variant is present in population databases (rs779101895, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 164 of the HRAS protein (p.Arg164Trp).
Sema4, Sema4 RCV002259010 SCV002537985 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-28 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005240496 SCV005886377 uncertain significance not specified 2025-02-05 criteria provided, single submitter clinical testing Variant summary: HRAS c.490C>T (p.Arg164Trp) results in a non-conservative amino acid change located in the small GTPase Ras family domain (IPR001806) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 248902 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.490C>T in individuals affected with Costello Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 579709). Based on the evidence outlined above, the variant was classified as uncertain significance.

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