ClinVar Miner

Submissions for variant NM_005159.5(ACTC1):c.475G>A (p.Asp159Asn) (rs397517063)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038330 SCV000062001 uncertain significance not specified 2013-01-09 criteria provided, single submitter clinical testing The Asp159Asn variant in ACTC1 has not previously been reported in the literatur e but has been identified in one individual with DCM (this individual's mother) tested by our laboratory (LMM unpublished data). This variant has not been ident ified in large and broad European American and African American populations by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/), though it may be common in other populations. Computational analyses (biochemical amino a cid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the A sp159Asn variant may impact the protein, though this information is not predicti ve enough to determine pathogenicity. In summary, additional information is need ed to fully assess the clinical significance of the Asp159Asn variant.
GeneDx RCV000157781 SCV000207711 likely pathogenic not provided 2014-07-09 criteria provided, single submitter clinical testing The D159N variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The D159N variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D159N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (P166A, Y168C) have been reported supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded.

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