ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.526G>A (p.Ala176Thr) (rs121918019)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000014677 SCV000678013 likely pathogenic Infantile hypophosphatasia 2014-01-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763299 SCV000893964 likely pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000808101 SCV000948193 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 176 of the ALPL protein (p.Ala176Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs121918019, ExAC 0.02%). This variant has been observed in combination with another ALPL variant in several individuals affected with hypophosphatasia (PMID: 25731960, 10679946, 11438998, 19232125). In addition, this variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with hypophosphatasia (PMID: 18559907). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 13683). Experimental studies have shown that this missense change has a deleterious effect on protein function (PMID: 10679946, 19500388). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000808101 SCV001250366 pathogenic not provided 2017-01-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000808101 SCV001476897 likely pathogenic not provided 2020-08-28 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity. Found in at least one patient with expected phenotype for this gene. Predicted to have a damaging effect on the protein. This variant is statistically more frequent in affected individuals than in the general population and/or healthy controls.
OMIM RCV000014677 SCV000034932 pathogenic Infantile hypophosphatasia 2008-09-01 no assertion criteria provided literature only
OMIM RCV000014678 SCV000034933 pathogenic Childhood hypophosphatasia 2008-09-01 no assertion criteria provided literature only
Natera, Inc. RCV001275108 SCV001459878 pathogenic Hypophosphatasia 2020-09-16 no assertion criteria provided clinical testing

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