ClinVar Miner

Submissions for variant NM_000091.4(COL4A3):c.4523A>G (p.Asn1508Ser) (rs200512461)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000337893 SCV000428194 uncertain significance Alport syndrome 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.
Counsyl RCV000673190 SCV000798365 uncertain significance Alport syndrome, autosomal recessive 2018-03-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825316 SCV000966611 uncertain significance not specified 2018-05-21 criteria provided, single submitter clinical testing The p.Asn1508Ser variant in COL4A3 has been reported in 1 Italian individual wit h end stage renal disease (ESRD), hematuria and proteinuria, who was also hetero zygous for a variant in another gene (COL4A4). The p.Asn1508Ser variant in COL4A 3 did not segregate in a sibling with hematuria and proteinuria, while the COL4 A4 variant was detected in that sibling (Fallerini 2017). This variant has also been identified in (52/126600) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs200512461). Althoug h this variant has been seen in the general population, its frequency is not hig h enough to rule out a pathogenic role. Computational prediction tools and conse rvation analysis do not provide strong support for or against an impact to the p rotein. In summary, the clinical significance of the p.Asn1508Ser variant is unc ertain. ACMG/AMP Criteria Applied: PM2_Supporting, BS4_Supporting.

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