ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.31G>A (p.Ala11Thr)

gnomAD frequency: 0.00001  dbSNP: rs727504496
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155632 SCV000205340 uncertain significance not specified 2016-03-25 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala11Thr vari ant in HRAS has been identified by our laboratory in 1 individual with clinical features of Noonan spectrum disorders and was inherited from a reportedly unaffe cted parent. This variant has been identified in 1/16464 of South Asian chromoso mes and 1/65720 of European chromosomes by the Exome Aggregation Consortium (ExA C, http://exac.broadinstitute.org; dbSNP rs727504496). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Ala1 1Thr variant is uncertain, these data suggest that it is more likely to be benig n.
Labcorp Genetics (formerly Invitae), Labcorp RCV000694918 SCV000823385 uncertain significance Costello syndrome 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 11 of the HRAS protein (p.Ala11Thr). This variant is present in population databases (rs727504496, gnomAD 0.003%). 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: 178860). 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.
Baylor Genetics RCV000694918 SCV001481472 uncertain significance Costello syndrome 2020-11-18 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics RCV004019863 SCV003563983 uncertain significance Cardiovascular phenotype 2021-04-28 criteria provided, single submitter clinical testing The c.31G>A (p.A11T) alteration is located in exon 2 (coding exon 1) of the HRAS gene. This alteration results from a G to A substitution at nucleotide position 31, causing the alanine (A) at amino acid position 11 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV000694918 SCV003811239 uncertain significance Costello syndrome 2019-03-20 criteria provided, single submitter clinical testing

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