ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.283G>A (p.Val95Met) (rs139811782)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001067182 SCV001232228 likely pathogenic not provided 2020-07-13 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 95 of the ALPL protein (p.Val95Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs139811782, ExAC 0.01%). This variant has been observed in individual(s) with hypophosphatasia (PMID: 31641588, 30719581). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 427763). 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: Not Available; PolyPhen-2: Probably Damaging; Align-GVGD: Not Available). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV001535923 SCV001752575 likely pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2021-06-30 criteria provided, single submitter clinical testing
Institute of Human Genetics,University of Wuerzburg RCV000490714 SCV000579348 likely pathogenic Low alkaline phosphatase no assertion criteria provided clinical testing
Natera, Inc. RCV001273158 SCV001455763 uncertain significance Hypophosphatasia 2020-09-16 no assertion criteria provided clinical testing

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