ClinVar Miner

Submissions for variant NM_018368.4(LMBRD1):c.1130T>C (p.Phe377Ser)

gnomAD frequency: 0.00050  dbSNP: rs73477459
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000518940 SCV000618025 uncertain significance not provided 2017-06-21 criteria provided, single submitter clinical testing The F377S variant in the LMBRD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The F377S variant is observed in 6/4738 (0.13%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). The F377S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret F377S as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001070769 SCV001236037 uncertain significance Methylmalonic aciduria and homocystinuria type cblF 2022-10-14 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 377 of the LMBRD1 protein (p.Phe377Ser). This variant is present in population databases (rs73477459, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with LMBRD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 449688). 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 expected to disrupt LMBRD1 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 RCV004639262 SCV005130560 uncertain significance Inborn genetic diseases 2024-03-15 criteria provided, single submitter clinical testing The c.1130T>C (p.F377S) alteration is located in exon 12 (coding exon 12) of the LMBRD1 gene. This alteration results from a T to C substitution at nucleotide position 1130, causing the phenylalanine (F) at amino acid position 377 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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