ClinVar Miner

Submissions for variant NM_031935.3(HMCN1):c.9929T>C (p.Leu3310Pro)

gnomAD frequency: 0.00036  dbSNP: rs148265876
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000408185 SCV000351904 uncertain significance Age related macular degeneration 1 2018-01-12 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001859764 SCV002175657 uncertain significance not provided 2024-12-24 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 3310 of the HMCN1 protein (p.Leu3310Pro). This variant is present in population databases (rs148265876, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with HMCN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 294217). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV004021394 SCV003694219 uncertain significance not specified 2021-09-16 criteria provided, single submitter clinical testing The c.9929T>C (p.L3310P) alteration is located in exon 65 (coding exon 65) of the HMCN1 gene. This alteration results from a T to C substitution at nucleotide position 9929, causing the leucine (L) at amino acid position 3310 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000408185 SCV004179865 uncertain significance Age related macular degeneration 1 2023-04-11 criteria provided, single submitter clinical testing

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