ClinVar Miner

Submissions for variant NM_001384474.1(LOXHD1):c.1605A>G (p.Ile535Met)

gnomAD frequency: 0.00003  dbSNP: rs770710016
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000618 SCV001157615 uncertain significance Autosomal recessive nonsyndromic hearing loss 77 2019-09-16 criteria provided, single submitter clinical testing The LOXHD1 c.1605A>G p.Ile535Met variant (rs770710016), to our knowledge, has not been reported in the medical literature or gene specific databases. This variant is found in the general population with an allele frequency in non-Finnish Europeans of 0.01% (9/77,580 alleles) in the Genome Aggregation Database. The isoleucine at codon 535 is moderately conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Based on the available information, the clinical significance of this variant is uncertain.
Athena Diagnostics RCV001289084 SCV001476664 uncertain significance not provided 2019-12-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001289084 SCV002190162 uncertain significance not provided 2022-09-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 535 of the LOXHD1 protein (p.Ile535Met). This variant is present in population databases (rs770710016, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LOXHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 811044). 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: "Benign"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Fulgent Genetics, Fulgent Genetics RCV001000618 SCV002788707 uncertain significance Autosomal recessive nonsyndromic hearing loss 77 2021-07-28 criteria provided, single submitter clinical testing
GeneDx RCV001289084 SCV003933360 uncertain significance not provided 2023-10-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004639428 SCV005136604 uncertain significance Inborn genetic diseases 2024-05-30 criteria provided, single submitter clinical testing The c.1605A>G (p.I535M) alteration is located in exon 12 (coding exon 12) of the LOXHD1 gene. This alteration results from a A to G substitution at nucleotide position 1605, causing the isoleucine (I) at amino acid position 535 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001000618 SCV002086332 uncertain significance Autosomal recessive nonsyndromic hearing loss 77 2020-03-04 no assertion criteria provided clinical testing

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