ClinVar Miner

Submissions for variant NM_001130144.3(LTBP3):c.2058C>A (p.Asn686Lys)

dbSNP: rs376337792
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520951 SCV000621633 uncertain significance not provided 2017-10-24 criteria provided, single submitter clinical testing The N686K variant in the LTBP3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not observed in the homozygous state, the N686K variant is observed in 47/30780 (0.15%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The N686K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N686K as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001858040 SCV002205297 uncertain significance Brachyolmia-amelogenesis imperfecta syndrome 2023-04-22 criteria provided, single submitter clinical testing 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 452796). This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. This variant is present in population databases (rs376337792, gnomAD 0.2%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 686 of the LTBP3 protein (p.Asn686Lys).
Ambry Genetics RCV002420324 SCV002727595 likely benign Inborn genetic diseases 2021-11-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity RCV000520951 SCV003812784 uncertain significance not provided 2022-11-22 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003962455 SCV004784613 likely benign LTBP3-related disorder 2022-09-28 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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