ClinVar Miner

Submissions for variant NM_001097577.3(ANG):c.61C>T (p.Pro21Ser)

gnomAD frequency: 0.00015  dbSNP: rs149672657
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000991532 SCV001143030 uncertain significance not provided 2018-09-18 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000991532 SCV001149111 uncertain significance not provided 2023-01-01 criteria provided, single submitter clinical testing ANG: PS4:Moderate
Invitae RCV000991532 SCV003035169 uncertain significance not provided 2023-11-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 21 of the ANG protein (p.Pro21Ser). This variant is present in population databases (rs149672657, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of ANG-related conditions (PMID: 17886298, 18087731, 22190368, 26551617). This variant is also known as P(-4)S. ClinVar contains an entry for this variant (Variation ID: 804533). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000991532 SCV003935640 uncertain significance not provided 2023-06-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22190368, 18087731, 17886298, 26551617)
PreventionGenetics, part of Exact Sciences RCV003413776 SCV004117189 uncertain significance ANG-related condition 2023-05-10 criteria provided, single submitter clinical testing The ANG c.61C>T variant is predicted to result in the amino acid substitution p.Pro21Ser. This variant (notated as P-4S or P(-4)S in older publications) has been reported in both amyotrophic lateral sclerosis patients and control individuals (Wu et al. 2007. PubMed ID: 17886298; van Es et al. 2011. PubMed ID: 22190368; Gellera et al. 2007. PubMed ID: 18087731). This variant is reported in 0.029% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-21161784-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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