ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.1823C>G (p.Pro608Arg) (rs41282932)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041259 SCV000064950 likely benign not specified 2015-02-06 criteria provided, single submitter clinical testing p.Pro608Arg in exon 18 of USH1C: This variant has been previously reported in 3 individuals with Usher syndrome or hearing loss and 2 individuals by our laborat ory; 3 of whom have another genetic etiology to explain their hearing loss (Crem ers 2007, Vera 2014, LMM unpublished data). This variant has also been identifie d in 0.1% (51/60306) of European chromosomes by the Exome Aggregation Consortium (ExAC,; dbSNP rs41282932). In summary, the prese nce of this variant in 3 individuals with another etiology for hearing loss and its frequency in the general population suggest that it is likely benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755427 SCV000605534 uncertain significance not provided 2018-05-25 criteria provided, single submitter clinical testing The p.Pro608Arg variant (rs41282932) has been identified in a homozygous state in a single induvial with non-syndromic hearing loss (Ouyang 2002). However it has been identified in several other cases with an alternate molecular basis for hearing loss, suggesting that it is not a causative variant (Cremers 2007, and Vona 2014). The p.Pro608Arg variant has also been reported to ClinVar (Variation ID: 5148). This variant is listed in the NHLBI GO Exome Sequencing Project with an overall population frequency of 0.06 percent (identified on 8 out of 12,984 chromosomes) and is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.05 percent (identified on 124 out of 267,276 chromosomes). The proline at position 608 is weakly conserved (considering 12 species) (Alamut v.2.8.1) and computational analyses of the effects of the p.Pro608Arg variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: possibly damaging). Altogether, there is not enough evidence to classify the p.Pro608Arg variant with certainty.
OMIM RCV000005455 SCV000025637 pathogenic Deafness, autosomal recessive 18 2002-07-01 no assertion criteria provided literature only
Natera, Inc. RCV001276292 SCV001462402 uncertain significance Usher syndrome, type 1C 2020-04-11 no assertion criteria provided clinical testing

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