ClinVar Miner

Submissions for variant NM_014053.4(FLVCR1):c.1158T>G (p.Ile386Met) (rs149834738)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522010 SCV000618705 uncertain significance not provided 2017-07-06 criteria provided, single submitter clinical testing The I386M variant in the FLVCR1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the I386M variant is observed in 18/16512 (0.11%) alleles from individuals of South Asian background in the ExAC dataset (Lek et al., 2016). The I386M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret I386M as a variant of uncertain significance.
Athena Diagnostics Inc RCV000522010 SCV001143947 uncertain significance not provided 2020-01-30 criteria provided, single submitter clinical testing
Invitae RCV000522010 SCV001224358 uncertain significance not provided 2020-05-20 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 386 of the FLVCR1 protein (p.Ile386Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs149834738, ExAC 0.1%). This variant has been observed in individual(s) with apparently non-syndromic retinitis pigmentosa (PMID: 30656474). ClinVar contains an entry for this variant (Variation ID: 450159). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). 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.
Illumina Clinical Services Laboratory,Illumina RCV001099906 SCV001256398 uncertain significance Posterior column ataxia-retinitis pigmentosa syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GenomeConnect - Invitae Patient Insights Network RCV001099906 SCV001749854 not provided Posterior column ataxia-retinitis pigmentosa syndrome no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 05-22-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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