Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002017827 | SCV002298580 | uncertain significance | not provided | 2021-01-26 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with serine at codon 76 of the SAMD9L protein (p.Asn76Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SAMD9L-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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. |
St. |
RCV002254743 | SCV002525939 | uncertain significance | Ataxia-pancytopenia syndrome | 2022-04-20 | criteria provided, single submitter | clinical testing | The SAMD9L c.227A>G (p.Asn76Ser) missense change in absent in gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org/). It is predicted to have a benign effect of this variant on protein function (BP4), but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with SAMD9L-associated conditions. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2, BP4. |
Gene |
RCV002017827 | SCV005375816 | uncertain significance | not provided | 2023-11-09 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV004970779 | SCV005497631 | uncertain significance | Inborn genetic diseases | 2024-10-17 | criteria provided, single submitter | clinical testing | The p.N76S variant (also known as c.227A>G), located in coding exon 1 of the SAMD9L gene, results from an A to G substitution at nucleotide position 227. The asparagine at codon 76 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |