ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.818C>T (p.Thr273Met) (rs148405563)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000710516 SCV000342299 uncertain significance not provided 2016-05-20 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000263557 SCV000354303 benign Hypophosphatasia 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000710516 SCV000566451 uncertain significance not provided 2017-02-03 criteria provided, single submitter clinical testing The T273M variant in the ALPL gene has been reported as a rare heterozygous variant associated with low serum alkaline phosphatase and low bone mineral density (Nielson et al., 2012). The T273M variant is observed in 141/66460 (0.21%) alleles from individuals of non-Finnish European background, including multiple unrelated homozygous individuals, in the ExAC dataset (Lek et al., 2016). The T273M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R272C, R272H, R272L, L275P) have been reported in the Human Gene Mutation Database in association with hypophosphatasia (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret L275P as a variant of uncertain significance.
Athena Diagnostics Inc RCV000710516 SCV000840754 benign not provided 2017-09-30 criteria provided, single submitter clinical testing
Invitae RCV000710516 SCV001110181 benign not provided 2020-12-08 criteria provided, single submitter clinical testing
Natera, Inc. RCV000263557 SCV001463897 benign Hypophosphatasia 2020-01-11 no assertion criteria provided clinical testing

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