ClinVar Miner

Submissions for variant NM_014845.6(FIG4):c.1879A>G (p.Thr627Ala)

dbSNP: rs762859144
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000456786 SCV000546069 uncertain significance Charcot-Marie-Tooth disease type 4 2022-07-25 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 627 of the FIG4 protein (p.Thr627Ala). This variant is present in population databases (rs762859144, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with FIG4-related conditions. ClinVar contains an entry for this variant (Variation ID: 407087). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Molecular Genetics Laboratory, London Health Sciences Centre RCV001172966 SCV001336041 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Ambry Genetics RCV002411446 SCV002722386 uncertain significance Inborn genetic diseases 2022-06-03 criteria provided, single submitter clinical testing The p.T627A variant (also known as c.1879A>G), located in coding exon 16 of the FIG4 gene, results from an A to G substitution at nucleotide position 1879. The threonine at codon 627 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004742423 SCV005345875 uncertain significance FIG4-related disorder 2024-04-25 no assertion criteria provided clinical testing The FIG4 c.1879A>G variant is predicted to result in the amino acid substitution p.Thr627Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.082% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-110098253-A-G). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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