ClinVar Miner

Submissions for variant NM_005876.5(SPEG):c.52C>T (p.Pro18Ser)

gnomAD frequency: 0.00019  dbSNP: rs544959269
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001944111 SCV002212251 uncertain significance not provided 2022-07-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 18 of the SPEG protein (p.Pro18Ser). This variant is present in population databases (rs544959269, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SPEG-related conditions. ClinVar contains an entry for this variant (Variation ID: 1432832). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 RCV002561425 SCV003687857 uncertain significance Inborn genetic diseases 2021-12-07 criteria provided, single submitter clinical testing The c.52C>T (p.P18S) alteration is located in exon 1 (coding exon 1) of the SPEG gene. This alteration results from a C to T substitution at nucleotide position 52, causing the proline (P) at amino acid position 18 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV003492703 SCV004237640 uncertain significance Myopathy, centronuclear, 5 2023-05-10 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV003151367 SCV003840077 uncertain significance not specified 2022-06-27 no assertion criteria provided clinical testing DNA sequence analysis of the SPEG gene demonstrated a sequence change, c.52C>T, in exon 1 that results in an amino acid change, p.Pro18Ser. This sequence change has been described in the gnomAD database with a frequency of 0.023% in the non-Finnish European subpopulation (dbSNP rs544959269). The p.Pro18Ser change affects a moderately conserved amino acid residue located in a domain of the SPEG protein that is not known to be functional. The p.Pro18Ser substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with SPEG-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro18Ser change remains unknown at this time.

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