ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.403C>G (p.Leu135Val)

gnomAD frequency: 0.00004  dbSNP: rs368450282
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000517385 SCV000612214 uncertain significance not specified 2017-05-17 criteria provided, single submitter clinical testing
Counsyl RCV000671911 SCV000796945 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2018-01-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002506248 SCV002816404 uncertain significance Diabetes mellitus, transient neonatal, 2; Hyperinsulinemic hypoglycemia, familial, 1; Leucine-induced hypoglycemia; Type 2 diabetes mellitus; Diabetes mellitus, permanent neonatal 3 2021-09-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002527449 SCV003440253 uncertain significance not provided 2022-10-05 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 135 of the ABCC8 protein (p.Leu135Val). This variant is present in population databases (rs368450282, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive diffuse congenital hyperinsulinism (PMID: 20685672). ClinVar contains an entry for this variant (Variation ID: 446772). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCC8 protein function. Experimental studies have shown that this missense change affects ABCC8 function (PMID: 30354297). 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.
Natera, Inc. RCV001272247 SCV001454049 uncertain significance Hereditary hyperinsulinism 2020-09-16 no assertion criteria provided clinical testing

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