ClinVar Miner

Submissions for variant NM_173630.4(RTTN):c.4877C>T (p.Thr1626Met)

gnomAD frequency: 0.00006  dbSNP: rs781683199
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000444631 SCV000532421 likely benign not specified 2018-02-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
CeGaT Center for Human Genetics Tuebingen RCV000996700 SCV001151564 uncertain significance not provided 2019-04-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV001333061 SCV001525546 uncertain significance Microcephalic primordial dwarfism due to RTTN deficiency 2019-01-03 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Invitae RCV000996700 SCV002220015 uncertain significance not provided 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1626 of the RTTN protein (p.Thr1626Met). This variant is present in population databases (rs781683199, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with RTTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 389771). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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