ClinVar Miner

Submissions for variant NM_001110556.2(FLNA):c.1664C>A (p.Thr555Lys)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV004529760 SCV004107317 uncertain significance FLNA-related disorder 2022-08-30 criteria provided, single submitter clinical testing The FLNA c.1664C>A variant is predicted to result in the amino acid substitution p.Thr555Lys. This variant was reported in an individual with otopalatodigital syndrome 2 (Robertson et al. 2003. PubMed ID: 12612583). This variant is reported in 0.0052% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-153593531-G-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004823149 SCV005586249 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2024-09-25 criteria provided, single submitter clinical testing The p.T555K variant (also known as c.1664C>A), located in coding exon 10 of the FLNA gene, results from a C to A substitution at nucleotide position 1664. The threonine at codon 555 is replaced by lysine, an amino acid with similar properties. This variant has been reported in a female with cleft palate (Robertson SP et al. Nat Genet, 2003 Apr;33:487-91). Based on data from gnomAD, the A allele has an overall frequency of <0.01% (1/181657) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was <0.01% (1/19069) of South Asian alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV005228025 SCV005863988 benign Heterotopia, periventricular, X-linked dominant; Melnick-Needles syndrome; Oto-palato-digital syndrome, type II; Frontometaphyseal dysplasia 2024-08-20 criteria provided, single submitter clinical testing

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