ClinVar Miner

Submissions for variant NM_003172.4(SURF1):c.574C>T (p.Arg192Trp) (rs782190413)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199387 SCV000252352 pathogenic not provided 2018-07-25 criteria provided, single submitter clinical testing The R192W missense mutation has been reported previously in a patient with Leigh syndrome. Furthermore, other missense mutations at the same position (R192Q, R192G) have also been reported as pathogenic.
Invitae RCV000631410 SCV000752482 pathogenic Leigh syndrome 2017-12-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 192 of the SURF1 protein (p.Arg192Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs782190413, ExAC 0.002%). This variant has been reported in the compound heterozygous state with a second SURF1 variant in multiple individuals affected with Leigh syndrome (PMID: 12515039, 27896082, 19780766) and in an individual affected with Charcot-Marie-Tooth disease, type 4 (CMT4) (PMID: 24027061). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 215235). 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"). Other missense substitutions at this codon (p.Arg192Gln and p.Arg192Gly) have been reported in individuals affected with Leigh syndrome (PMID: 23829769, 16542579). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000202523 SCV000257493 pathogenic Charcot-Marie-Tooth disease, type 4k 2013-10-22 no assertion criteria provided literature only

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