ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.1918GAA[1] (p.Glu641del)

dbSNP: rs786203970
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167505 SCV000218363 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-22 criteria provided, single submitter clinical testing The c.1921_1923delGAA variant (also known as p.E641del) is located in coding exon 4 of the MSH6 gene. This variant results from an in-frame GAA deletion at nucleotide positions 1921 to 1923. This results in the in-frame deletion of a glutamic acid at codon 641. This variant was reported in one Puerto Rican patient with breast cancer who previously tested negative for BRCA1/2 mutations (Dutil J et al. Sci Rep, 2019 11;9:17769). The deleted amino acid position is poorly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000629967 SCV000750923 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-17 criteria provided, single submitter clinical testing This variant, c.1921_1923del, results in the deletion of 1 amino acid(s) of the MSH6 protein (p.Glu641del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs762299881, gnomAD 0.003%). This variant has been observed in individual(s) with breast cancer (PMID: 31780696). ClinVar contains an entry for this variant (Variation ID: 187749). 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 RCV000167505 SCV000911467 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-09 criteria provided, single submitter clinical testing This variant causes an in-frame deletion of one amino acid of the MSH6 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 31780696). This variant has been identified in 1/245838 chromosomes 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800507 SCV002047309 uncertain significance not provided 2021-03-02 criteria provided, single submitter clinical testing
GeneDx RCV001800507 SCV002526277 uncertain significance not provided 2022-06-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Identified in a patient with breast cancer (Dutil 2019); This variant is associated with the following publications: (PMID: 31780696, 17531815, 21120944)
All of Us Research Program, National Institutes of Health RCV003995596 SCV004835589 uncertain significance Lynch syndrome 2023-11-20 criteria provided, single submitter clinical testing This variant causes an in-frame deletion of one amino acid of the MSH6 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 31780696). This variant has been identified in 1/245838 chromosomes 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.
Baylor Genetics RCV004567353 SCV005054899 uncertain significance Endometrial carcinoma 2024-02-23 criteria provided, single submitter clinical testing

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