ClinVar Miner

Submissions for variant NM_000371.3(TTR):c.88T>C (p.Cys30Arg) (rs121918083)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000014386 SCV000696637 likely pathogenic Amyloidogenic transthyretin amyloidosis 2016-04-05 criteria provided, single submitter clinical testing Variant Summary: The c.88T>C variant involves the alteration of a conserved nucleotide and 4/4 in silico tools predict a pathogenic outcome. The variant, also known as Cys10Arg, involves the only free Cysteine in TTR and is hypothesized to cause structural changes in the heterozygous TTR dimer and tetramer that lead to polymerization of TTR molecules (Uemichi_1992). The variant is absent from the large, broad ExAC control population. The variant was found in multiple affected individuals in the literature, including a family in which all tested affected males carried the variant while three unaffected females also carried the variant, suggesting some role of sex in the occurrence of disease (Uemichi_1992). One clinical lab has classified the variant as "pathogenic". Therefore, taken together, this variant has been classified as Likely Pathogenic.
Athena Diagnostics Inc RCV000993524 SCV001146566 uncertain significance not provided 2018-09-10 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000993524 SCV001501203 pathogenic not provided 2020-08-01 criteria provided, single submitter clinical testing
Invitae RCV000014386 SCV001575268 likely pathogenic Amyloidogenic transthyretin amyloidosis 2020-01-13 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 30 of the TTR protein (p.Cys30Arg). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 1362222, 24664531, Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as Cys10Arg in the literature. ClinVar contains an entry for this variant (Variation ID: 13444). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Not Available; PolyPhen-2: Probably Damaging; Align-GVGD: Not Available). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000014386 SCV000034635 pathogenic Amyloidogenic transthyretin amyloidosis 1992-12-01 no assertion criteria provided literature only

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