ClinVar Miner

Submissions for variant NM_000193.4(SHH):c.424G>A (p.Glu142Lys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003021868 SCV003321187 uncertain significance Holoprosencephaly 3 2022-02-19 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SHH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 142 of the SHH protein (p.Glu142Lys).
Human Genetics Section, Sidra Medicine RCV003021868 SCV004708148 likely pathogenic Holoprosencephaly 3 2024-02-28 criteria provided, single submitter research Variant is predicted to result in a missense amino acid change from glutamine to lysine. ClinVar contains an entry for this variant (Variation ID: 2099748). The de novo variant is present in a patient with holoprosencephaly, cleft lip and palate, and microphthalmia.This variant was determined to be likely pathogenic according to ACMG Guidelines

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