ClinVar Miner

Submissions for variant NM_000371.4(TTR):c.13C>T (p.Arg5Cys)

gnomAD frequency: 0.00005  dbSNP: rs144792001
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001210254 SCV001381733 uncertain significance Amyloidosis, hereditary systemic 1 2023-02-10 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 5 of the TTR protein (p.Arg5Cys). This variant is present in population databases (rs144792001, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with TTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 940630). 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. 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 RCV002393475 SCV002697729 uncertain significance Cardiovascular phenotype 2022-01-11 criteria provided, single submitter clinical testing The p.R5C variant (also known as c.13C>T), located in coding exon 1 of the TTR gene, results from a C to T substitution at nucleotide position 13. The arginine at codon 5 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected in a patient with late onset hypertrophic cardiomyopathy and mild polyneuropathy at 81 years due to ATTR amyloidosis (Auer-Grumbach M et al. J Clin Med, 2020 Jul;9:). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002480694 SCV002778044 uncertain significance Hyperthyroxinemia, dystransthyretinemic; Amyloidosis, hereditary systemic 1; Carpal tunnel syndrome 1 2021-09-23 criteria provided, single submitter clinical testing

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