ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.40G>A (p.Ala14Thr)

dbSNP: rs876658277
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216179 SCV000273304 uncertain significance Hereditary cancer-predisposing syndrome 2015-01-05 criteria provided, single submitter clinical testing The p.A14T variant (also known as c.40G>A), located in coding exon 1 of the MSH2 gene, results from a G to A substitution at nucleotide position 40. The alanine at codon 14 is replaced by threonine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project; however this position was not covered in the ESP. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 42000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. This alteration is predicted to be benign and tolerated by PolyPhen and SIFT in silico analyses, respectively. In addition, this alteration is predicted to be benign by MAPP-MMR in silico analyses (Chao E et al. Hum Mutat. 2008 Jun;29(6):852-60). Since supporting evidence is limited at this time, the clinical significance of p.A14T remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000558623 SCV000625424 benign Hereditary nonpolyposis colorectal neoplasms 2023-07-07 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000216179 SCV000911693 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-10 criteria provided, single submitter clinical testing
GeneDx RCV001770169 SCV001992283 uncertain significance not provided 2019-04-18 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge

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