ClinVar Miner

Submissions for variant NM_001097577.3(ANG):c.3G>A (p.Met1Ile)

gnomAD frequency: 0.00020  dbSNP: rs201068740
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000995107 SCV001149109 uncertain significance not provided 2024-01-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001112905 SCV001270619 uncertain significance Amyotrophic lateral sclerosis type 9 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx RCV000995107 SCV001986295 uncertain significance not provided 2020-08-28 criteria provided, single submitter clinical testing Previously identified in individuals with PD, ALS and/or FTLD; one of these individuals who was heterozygous for c.3G>T, which also leads to an M1? varinat, also harbored a pathogenic variant in the SOD1 gene (van Es, et al., 2011; Conforti, et al., 2008; Gellera et al., 2008; Tripolszki et al., 2019); Variant is located within the signal peptide and affecting the start codon, which may influence the correct translation of the protein; ; however, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. .; This variant is associated with the following publications: (PMID: 22190368, 17703939, 28444446, 18087731, 31025543)
Invitae RCV000995107 SCV002436225 likely benign not provided 2024-01-11 criteria provided, single submitter clinical testing
Human Genetics Bochum, Ruhr University Bochum RCV002463771 SCV002758563 uncertain significance Amyotrophic lateral sclerosis type 10 2022-10-21 criteria provided, single submitter clinical testing ACMG criteria used to clasify this variant: PVS1, PM2
PreventionGenetics, part of Exact Sciences RCV003413785 SCV004116503 uncertain significance ANG-related disorder 2024-02-15 criteria provided, single submitter clinical testing The ANG c.3G>A variant is predicted to disrupt the translation initiation site (Start Loss). This variant, which is located in the signal peptide region and has been previously described in the literature as Met-24Ile, has been reported in patients with sporadic amyotrophic lateral sclerosis (ALS), Parkinson disease/parkinsonism, or frontotemporal dementia (Conforti et al. 2008. PubMed ID: 17703939; Gellera et al. 2008. PubMed ID: 18087731; van Es et al. 2011. PubMed ID: 22190368; Marjanović et al. 2017. PubMed ID: 28444446; Ungaro et al. 2020. PubMed ID: 32951934). To our knowledge, functional studies have not been performed to better understand the biological relevance of this variant. This variant is reported in 0.097% of alleles in individuals of Ashkenazi Jewish descent, and 0.022% overall in gnomAD, which may be too common to be a primary cause of disease. 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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