ClinVar Miner

Submissions for variant NM_001614.5(ACTG1):c.773C>T (p.Pro258Leu)

dbSNP: rs11549191
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791808 SCV000931071 uncertain significance Autosomal dominant nonsyndromic hearing loss 20; Baraitser-winter syndrome 2 2020-04-01 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 258 of the ACTG1 protein (p.Pro258Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in individual(s) with hearing impairment (PMID: 28000701). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 639093).
Athena Diagnostics Inc RCV000991480 SCV001142905 pathogenic not provided 2019-01-21 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/281966 chr). Predicted to have a damaging effect on the protein. One de novo case with parental identity confirmed.
CeGaT Center for Human Genetics Tuebingen RCV000991480 SCV001247664 pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing
GeneDx RCV000991480 SCV001782645 pathogenic not provided 2022-01-26 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); 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: 28000701)

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