ClinVar Miner

Submissions for variant NM_000409.4(GUCA1A):c.149C>T (p.Pro50Leu) (rs104893968)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444625 SCV000513203 uncertain significance not provided 2017-01-03 criteria provided, single submitter clinical testing The P50L variant in the GUCA1A gene has been reported previously in three members of a family with variable ocular abnormalities, ranging from minimal macular involvement to moderately severe cone-rod dystrophy (Downes et al., 2001). The P50L variant was also identified in a patient with cone and cone-rod dystrophy, however, informative familial segregation data was not included to confirm if this variant occurred de novo or was inherited in this individual (Boulanger-Scemama et al., 2015). The NHLBI ESP Exome Sequencing Project reports P50L was observed in 0.12% (10/8600) alleles from individuals of European American ancestry, indicating it may be a rare (benign) variant in this population. The P50L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. One in vitro functional study concluded that this variant results in impaired calcium binding, however, enzyme assays showed similar results for the P50L variant compared to wild type enzyme, and it is unclear how this variant impacts the protein function (Sokal et al., 2000). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We now interpret P50L as a variant of uncertain significance.
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787609 SCV000926593 pathogenic Macular dystrophy 2018-04-01 no assertion criteria provided research
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787610 SCV000926594 pathogenic Usher syndrome 2018-04-01 no assertion criteria provided research
OMIM RCV000009722 SCV000029941 pathogenic Cone dystrophy 3 2001-01-01 no assertion criteria provided literature only

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