ClinVar Miner

Submissions for variant NM_000032.5(ALAS2):c.508C>T (p.Arg170Cys)

dbSNP: rs1557248142
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001581864 SCV001817985 pathogenic not provided 2019-10-04 criteria provided, single submitter clinical testing Published functional studies demonstrate a decrease enzymatic activity of mutant protein when compared with WT protein (Ohba et al., 2013); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22983749, 19731322, 28102861)
Labcorp Genetics (formerly Invitae), Labcorp RCV001581864 SCV003445387 pathogenic not provided 2023-12-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 170 of the ALAS2 protein (p.Arg170Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with X-linked recessive congenital sideroblastic anemia (PMID: 19731322, 22983749, 28102861). This variant is also known as c.397C>T (p.R133C). ClinVar contains an entry for this variant (Variation ID: 1214130). 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 ALAS2 protein function. Experimental studies have shown that this missense change affects ALAS2 function (PMID: 22983749). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV001581864 SCV003829455 likely pathogenic not provided 2022-09-14 criteria provided, single submitter clinical testing

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