Submissions for variant NM_003172.4(SURF1):c.809_826dup (p.Glu270_Ile275dup)

dbSNP: rs782161777

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000689337	SCV000816983	uncertain significance	Leigh syndrome	2021-09-01	criteria provided, single submitter	clinical testing	This variant, c.809_826dup, results in the insertion of 6 amino acid(s) to the SURF1 protein (p.Glu270_Ile275dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with Leigh syndrome (PMID: 28429146). This variant is also known as c.826_827ins18. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000689337	SCV002548264	pathogenic	Leigh syndrome	2024-08-20	criteria provided, single submitter	clinical testing	Variant summary: SURF1 c.809_826dup18 (p.Glu270_Ile275dup) results in an in-frame duplication that is predicted to duplicate 6 amino acids into the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 246342 control chromosomes. c.809_826dup18 has been reported in the literature in compound heterozygous individuals affected with Leigh Syndrome (Ogawa_2017, Li_2018). It was also reported in an affected individual who was homozygous for a different SURF1 variant (Gilhooley_2024). These data indicate that the variant may be associated with disease. One publication shows that the variant is unable to rescue Complex IV formation in a SURF1 deficient cell assay when compared to wild-type SURF1 (Li_2018). The following publications have been ascertained in the context of this evaluation (PMID: 29933018, 28429146, 38397177, 31967322). ClinVar contains an entry for this variant (Variation ID: 520390). Based on the evidence outlined above, the variant was classified as pathogenic.
Laboratory of Metabolic Disorders, Peking University First Hospital	RCV000689337	SCV000732899	pathogenic	Leigh syndrome	2018-04-05	no assertion criteria provided	research