ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1858G>A (p.Asp620Asn)

gnomAD frequency: 0.00004  dbSNP: rs200337887
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000802810 SCV000942655 uncertain significance not provided 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 620 of the MSH3 protein (p.Asp620Asn). This variant is present in population databases (rs200337887, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 648147). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV001013421 SCV001174004 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-09 criteria provided, single submitter clinical testing The p.D620N variant (also known as c.1858G>A), located in coding exon 13 of the MSH3 gene, results from a G to A substitution at nucleotide position 1858. The aspartic acid at codon 620 is replaced by asparagine, 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.
Genetic Services Laboratory, University of Chicago RCV001816867 SCV002065302 uncertain significance not specified 2021-05-26 criteria provided, single submitter clinical testing DNA sequence analysis of the MSH3 gene demonstrated a sequence change, c.1858G>A, in exon 13 that results in an amino acid change, p.Asp620Asn. This sequence change has been described in the gnomAD database with a frequency of 0.065% in the East Asian subpopulation (dbSNP rs200337887). The p.Asp620Asn change affects a highly conserved amino acid residue located in a domain of the MSH3 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Asp620Asn substitution. This sequence change does not appear to have been previously described in patients with MSH3-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Asp620Asn change remains unknown at this time.
Sema4, Sema4 RCV001013421 SCV002535997 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-29 criteria provided, single submitter curation
GeneDx RCV000802810 SCV002588025 uncertain significance not provided 2022-04-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in a patient with lymphoblastic leukemia (Xue 2022); This variant is associated with the following publications: (PMID: 34608827)
Baylor Genetics RCV003467392 SCV004196976 uncertain significance Endometrial carcinoma 2024-03-21 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005036167 SCV005666193 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-03-01 criteria provided, single submitter clinical testing

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