ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.2629G>C (p.Ala877Pro)

dbSNP: rs377046577
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001369416 SCV001565855 uncertain significance Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2022-01-07 criteria provided, single submitter clinical testing 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. 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 not expected to disrupt FLNA protein function. ClinVar contains an entry for this variant (Variation ID: 1060042). This variant has not been reported in the literature in individuals affected with FLNA-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 877 of the FLNA protein (p.Ala877Pro).
Ambry Genetics RCV002438861 SCV002745693 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-03-23 criteria provided, single submitter clinical testing The p.A877P variant (also known as c.2629G>C), located in coding exon 17 of the FLNA gene, results from a G to C substitution at nucleotide position 2629. The alanine at codon 877 is replaced by proline, an amino acid with highly similar properties. Based on data from gnomAD, the C allele has an overall frequency of 0.0011% (2/181304) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.0037% (1/27377) of Latin American alleles. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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