ClinVar Miner

Submissions for variant NM_007373.4(SHOC2):c.1592A>G (p.His531Arg)

dbSNP: rs1848567648
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813699 SCV002060878 uncertain significance Noonan syndrome and Noonan-related syndrome 2018-04-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003401732 SCV004103716 uncertain significance SHOC2-related disorder 2023-08-31 criteria provided, single submitter clinical testing The SHOC2 c.1592A>G variant is predicted to result in the amino acid substitution p.His531Arg. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp RCV003539413 SCV004275692 uncertain significance RASopathy 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 531 of the SHOC2 protein (p.His531Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SHOC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1334284). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SHOC2 protein function. 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.
Ambry Genetics RCV004040938 SCV005026127 uncertain significance Cardiovascular phenotype 2023-10-01 criteria provided, single submitter clinical testing The p.H531R variant (also known as c.1592A>G), located in coding exon 8 of the SHOC2 gene, results from an A to G substitution at nucleotide position 1592. The histidine at codon 531 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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