ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.492A>C (p.Lys164Asn)

gnomAD frequency: 0.00001  dbSNP: rs765014361
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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 RCV000558829 SCV000625170 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-12-08 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 455440). This missense change has been observed in individual(s) with glioblastoma (PMID: 31160353). This variant is present in population databases (rs765014361, gnomAD 0.002%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 164 of the MLH1 protein (p.Lys164Asn). 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 MLH1 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.
Color Diagnostics, LLC DBA Color Health RCV000580253 SCV000684836 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580253 SCV002646419 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-11 criteria provided, single submitter clinical testing The p.K164N variant (also known as c.492A>C), located in coding exon 6 of the MLH1 gene, results from an A to C substitution at nucleotide position 492. The lysine at codon 164 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Cure Brain Cancer Foundation Neuro-Oncology Group, Adult Cancer Program, University of New South Wales RCV000580253 SCV000902257 likely pathogenic Hereditary cancer-predisposing syndrome 2019-03-01 no assertion criteria provided research

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