ClinVar Miner

Submissions for variant NM_000492.3(CFTR):c.508C>T (p.Arg170Cys) (rs578029902)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526413 SCV000625754 uncertain significance Cystic fibrosis 2017-04-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 170 of the CFTR protein (p.Arg170Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs578029902, ExAC 0.02%). This variant has been reported in individuals affected with congenital absence of the vas deferens (PMID: 24958810) and chronic sinusitis (PMID: 15126740), however a second variant in CFTR was not identified in these individuals. It has also been observed with a pathogenic CFTR variant in an individual affected with alcohol-related pancreatitis (PMID: 14526128). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Integrated Genetics/Laboratory Corporation of America RCV000590353 SCV000697031 uncertain significance not provided 2016-01-04 criteria provided, single submitter clinical testing Variant summary: This c.508C>T variant affects a conserved nucleotide, resulting in non-conservative amino acid change from Arg to Cys. 5/5 in-silico tools predict this variant to be damaging. This variant was found in 7/120084 control chromosomes (including ExAC) at a frequency of 0.0000583, which does not significantly exceed maximal expected frequency of a pathogenic allele (0.0129603) in this gene based on the disease prevalence of cystic fibrosis. The variant has been found in patients with alcohol-related pancreatitis (n=2), Atypical Chronic Sinusitis (n=1), and CBAVD (n=1). In one alcohol-related pancreatitis, a known pathogenic mutation p.Phe508del was also found in heterozygous state. In the CBAVD patient, no pathogenic mutation was identified in the second allele. Thus, the variants role in causation of these phenotypes remains to be further clarified. Taken together, this variant has currently been classified as a Variant of Uncertain Significance.
Counsyl RCV000526413 SCV000792509 uncertain significance Cystic fibrosis 2017-06-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001023517 SCV001185415 uncertain significance Inborn genetic diseases 2019-12-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence

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