ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.1171del (p.Arg391fs)

dbSNP: rs751404811
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779691 SCV000916441 likely pathogenic Hypophosphatasia 2018-08-09 criteria provided, single submitter clinical testing Variant summary: ALPL c.1171delC (p.Arg391ValfsX12) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.4e-05 in 246250 control chromosomes (gnomAD). The variant, c.1171delC, has been reported in the literature in individuals affected with Hypophosphatasia (McKiernan_2017, Taillandier_1998). These data suggest the variant may be associated with Hypophosphatasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae RCV001232736 SCV001405304 pathogenic not provided 2023-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg391Valfs*12) in the ALPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALPL are known to be pathogenic (PMID: 3174660, 10679946, 32973344, 33814268). This variant is present in population databases (rs779683021, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with hypophosphatasia (PMID: 10094560). This variant is also known as 1172delC. ClinVar contains an entry for this variant (Variation ID: 632628). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV001253674 SCV001429514 uncertain significance Adult hypophosphatasia 2017-10-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001536120 SCV001752836 pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2021-06-30 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV001536120 SCV002060021 pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2021-11-08 criteria provided, single submitter clinical testing NM_000478.4(ALPL):c.1171delC(R391Vfs*12) is a frameshifting truncation variant classified as pathogenic in the context of hypophosphatasia. R391Vfs*12 has been observed in cases with relevant disease (PMID: 32160374). Functional assessments of this variant are available in the literature (PMID: 32160374). R391Vfs*12 has been observed in population frequency databases (gnomAD: NFE 0.005%). In summary, NM_000478.4(ALPL):c.1171delC(R391Vfs*12) is a frameshifting truncation variant in a gene where loss of function is a known mechanism of disease, is predicted to disrupt protein function, and has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Baylor Genetics RCV001253674 SCV004194430 pathogenic Adult hypophosphatasia 2023-09-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV000779691 SCV001459885 likely pathogenic Hypophosphatasia 2020-09-16 no assertion criteria provided clinical testing

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