ClinVar Miner

Submissions for variant NM_001370658.1(BTD):c.523A>G (p.Asn175Asp)

gnomAD frequency: 0.00001  dbSNP: rs397514370
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000021942 SCV000800562 uncertain significance Biotinidase deficiency 2017-07-17 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000727575 SCV000854816 likely pathogenic not provided 2018-01-03 criteria provided, single submitter clinical testing
Invitae RCV000021942 SCV001391009 pathogenic Biotinidase deficiency 2022-04-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 195 of the BTD protein (p.Asn195Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 9396567, 11865279). ClinVar contains an entry for this variant (Variation ID: 25021). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Asn195 amino acid residue in BTD. Other variant(s) that disrupt this residue have been observed in individuals with BTD-related conditions (PMID: 17185019), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002298448 SCV002598711 uncertain significance not specified 2022-09-27 criteria provided, single submitter clinical testing Variant summary: BTD c.523A>G (p.Asn175Asp) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251454 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.523A>G has been reported in the literature in an individual affected with Biotinidase Deficiency (example: Pomponio_1997). This information is insufficient to allow any conclusion about the variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=1) and pathogenic/likely pathogenic (n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV000021942 SCV002081555 pathogenic Biotinidase deficiency 2021-04-20 no assertion criteria provided clinical testing

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