ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.7779_7780insTTCGGGG (p.Val2594fs) (rs1557175195)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521545 SCV000622077 likely pathogenic not provided 2017-11-07 criteria provided, single submitter clinical testing Although the c.7755_7756insTTCGGGG variant in the FLNA gene has not been reported to our knowledge, this variant causes a shift in reading frame starting at codon valine 2586, changing it to a phenylalanine, and replaces the last 54 amino acids with 157 incorrect amino acids, thus altering and extending the resulting protein product. Other frameshift variants in the FLNA gene that extend the protein have been reported in Human Gene Mutation Database in association with PH (Stenson et al., 2014). Furthermore, the c.7755_7756insTTCGGGG variant has not been observed in large population cohorts (Lek et al., 2016).
Invitae RCV000536029 SCV000639838 pathogenic Periventricular nodular heterotopia 1; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2019-09-25 criteria provided, single submitter clinical testing While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 54 amino acids of the FLNA protein and is expected to extend the length of the FLNA protein by 104 additional residues. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with clinical features of FLNA-related disorders in a family (Invitae). ClinVar contains an entry for this variant (Variation ID: 453200). This variant results in an extension of the FLNA protein. Other variant(s) that result in a similarly extended protein product (p.Glu2617Valfs*124) have been determined to be pathogenic (Invitae). This suggests that these extensions are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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