ClinVar Miner

Submissions for variant NM_024596.5(MCPH1):c.1679G>T (p.Ser560Ile)

gnomAD frequency: 0.00010  dbSNP: rs201405704
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000146276 SCV000193542 uncertain significance Microcephaly 1, primary, autosomal recessive 2013-09-27 criteria provided, single submitter clinical testing
GeneDx RCV000523239 SCV000617181 uncertain significance not provided 2023-07-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV000146276 SCV000897468 uncertain significance Microcephaly 1, primary, autosomal recessive 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000523239 SCV003278460 uncertain significance not provided 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 560 of the MCPH1 protein (p.Ser560Ile). This variant is present in population databases (rs201405704, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MCPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 158822). 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) performed at Invitae indicates that this missense variant is not expected to disrupt MCPH1 protein function with a negative predictive value of 80%. 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 RCV004639142 SCV005132631 uncertain significance Inborn genetic diseases 2024-03-28 criteria provided, single submitter clinical testing The c.1679G>T (p.S560I) alteration is located in exon 8 (coding exon 8) of the MCPH1 gene. This alteration results from a G to T substitution at nucleotide position 1679, causing the serine (S) at amino acid position 560 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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