ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.1118T>A (p.Met373Lys) (rs121964958)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000012804 SCV001139372 pathogenic Propionic acidemia 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000012804 SCV001580696 pathogenic Propionic acidemia 2020-10-09 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 373 of the PCCA protein (p.Met373Lys). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with propionic acidemia (PMID: 22033733, 10101253). It is also known as M348K. ClinVar contains an entry for this variant (Variation ID: 12024). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCCA protein function. Experimental studies have shown that this variant affects PCCA protein function (PMID: 10101253). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012804 SCV000033044 pathogenic Propionic acidemia 1999-03-30 no assertion criteria provided literature only

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