ClinVar Miner

Submissions for variant NM_000409.4(GUCA1A):c.526C>T (p.Leu176Phe) (rs794727777)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000179309 SCV000231539 uncertain significance not provided 2014-06-04 criteria provided, single submitter clinical testing
Invitae RCV000179309 SCV001391516 pathogenic not provided 2019-08-12 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 176 of the GUCA1A protein (p.Leu176Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenyalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with macular dystrophy/cone dystrophy in families (PMID: 28025326, 26766544). ClinVar contains an entry for this variant (Variation ID: 198078). This variant has been reported to affect GUCA1A protein function (PMID: 28025326). For these reasons, this variant has been classified as Pathogenic.
SIB Swiss Institute of Bioinformatics RCV001251248 SCV001426750 uncertain significance Cone dystrophy 3 2020-06-05 criteria provided, single submitter curation This variant is interpreted as a variant of uncertain significance for macular dystrophy, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Prevalence in affected individuals statistically increased over controls (PS4 downgraded to supporting); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting).

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