ClinVar Miner

Submissions for variant NM_000440.3(PDE6A):c.878C>T (p.Pro293Leu) (rs114973968)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000178770 SCV000230924 benign not specified 2015-04-10 criteria provided, single submitter clinical testing
Invitae RCV000954915 SCV001101582 likely benign not provided 2020-12-03 criteria provided, single submitter clinical testing
Mendelics RCV000787859 SCV001137003 benign Retinitis pigmentosa 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000787859 SCV001315121 uncertain significance Retinitis pigmentosa 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet RCV000787859 SCV000926874 likely pathogenic Retinitis pigmentosa 2018-04-01 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000954915 SCV001553642 likely benign not provided no assertion criteria provided clinical testing The PDE6A p.Pro293Leu variant was identified in the literature in two patients with retinitis pigementosa: in one case the variant was identfiied as a heterozygous variant with no second variant identified, and in the second case the variant was identified as a homozygous variant however the patient was also homozygous for the known pathogenic p.Val685Met variant (Dryja_1999_PMID: 10393062 and Anasagasti_2013_PMID: 24416769). The variant was identified in dbSNP (ID: rs114973968) and ClinVar (classified as benign by EGL Genetic Diagnostics and Mendelics, as likely benign by Invitae, and as likely pathogenic by Medical Genetics Laboratory Kennedy Center). The variant was identified in control databases in 904 of 282780 chromosomes (1 homozygous) at a frequency of 0.003197 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 666 of 129142 chromosomes (freq: 0.005157), Other in 17 of 7226 chromosomes (freq: 0.002353), Latino in 81 of 35432 chromosomes (freq: 0.002286), South Asian in 65 of 30598 chromosomes (freq: 0.002124), European (Finnish) in 31 of 25114 chromosomes (freq: 0.001234), East Asian in 20 of 19952 chromosomes (freq: 0.001002), African in 20 of 24950 chromosomes (freq: 0.000802), and Ashkenazi Jewish in 4 of 10366 chromosomes (freq: 0.000386). Although the p.Pro293 residue is not conserved in mammals and other organisms, computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics,Academic Medical Center RCV000178770 SCV001918169 benign not specified no assertion criteria provided clinical testing

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