ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1000C>T (p.Leu334Phe)

dbSNP: rs2082990641
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001192212 SCV001360238 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 334 of the MLH1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MLH1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001192212 SCV002637325 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-16 criteria provided, single submitter clinical testing The p.L334F variant (also known as c.1000C>T), located in coding exon 11 of the MLH1 gene, results from a C to T substitution at nucleotide position 1000. The leucine at codon 334 is replaced by phenylalanine, an amino acid with highly 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.

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