ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.542C>T (p.Ser181Leu) (rs199590449)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169128 SCV000220338 likely pathogenic Infantile hypophosphatasia 2014-05-21 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000729215 SCV000856857 likely pathogenic not provided 2017-09-12 criteria provided, single submitter clinical testing
Invitae RCV000729215 SCV001210953 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 181 of the ALPL protein (p.Ser181Leu). The serine residue is moderately conserved and there is large physicochemical difference between serine and leucine. This variant is present in population databases (rs199590449, ExAC 0.006%). This variant has been observed in individuals with hypophosphatasia (PMID: 11479741, 17253930, 16583935, 32160374). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as S164L in the literature. ClinVar contains an entry for this variant (Variation ID: 188798). This variant has been reported to affect ALPL protein function (PMID: 11479741). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196302 SCV001366893 likely pathogenic Adult hypophosphatasia 2018-11-07 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PM1,PM2,PP2,PP5.
GeneDx RCV000729215 SCV001814029 likely pathogenic not provided 2021-04-20 criteria provided, single submitter clinical testing Observed as heterozygous with and without another ALPL variant in patients with hypophosphatasia in published literature (Spentchian et al., 2006; Nielson et al., 2012; Tenorio et al., 2017; Del Angel et al., 2020; Jandl et al., 2021); Published functional studies demonstrate a damaging effect on enzyme activity (Lia-Baldini et al., 2001); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 11479741, 16583935, 32160374, 31589614, 33601892, 33549410, 33191482, 17253930, 26783040, 21956185, 28127875)

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