ClinVar Miner

Submissions for variant GRCh38/hg38 14q11.2(chr14:21287774-21294830)x3

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV003327692 SCV004034223 likely pathogenic Cone-rod dystrophy 13 2023-08-24 criteria provided, single submitter research A maternally inherited heterozygous duplication of exons 2-3 in RPGRIP1 (NM_020366.4) was identified by exome sequencing in one individual with cone-rod dystrophy in the compound heterozygous state, along with a variant of uncertain significance (p.Val1265GlyfsTer19 ) (Variation ID: 814009), ([GRCh 38] chr14:21287774_21294830x3)(PMID: 30072743). The presence of this duplication was validated by qPCR. These breakpoints have been estimated by exome sequencing and therefore may not reflect the true breakpoints. qPCR supports that this intragenic duplication is in tandem (PMID: 30072743). The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. This intragenic variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at exon 2 and leads to a premature termination codon. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of RPGRIP1 is an established disease mechanism in autosomal recessive cone-rod dystrophy ( In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive cone-rod dystrophy. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.9 points, 4-5: 0.08 points; Total: 0.98 points; Riggs 2020 (PMID: 31690835).

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