ClinVar Miner

Submissions for variant NM_005334.3(HCFC1):c.4910C>T (p.Ala1637Val)

gnomAD frequency: 0.00002  dbSNP: rs1002620023
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478950 SCV000573327 uncertain significance not provided 2017-02-22 criteria provided, single submitter clinical testing The A1637V variant in the HCFC1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1637V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A1637V as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002526949 SCV003499537 uncertain significance Methylmalonic acidemia with homocystinuria, type cblX 2022-01-18 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 423609). This variant has not been reported in the literature in individuals affected with HCFC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1637 of the HCFC1 protein (p.Ala1637Val).

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