Submissions for variant NM_058216.3(RAD51C):c.211A>T (p.Asn71Tyr)

dbSNP: rs876659936

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000220314	SCV000276903	uncertain significance	Hereditary cancer-predisposing syndrome	2021-05-04	criteria provided, single submitter	clinical testing	The p.N71Y variant (also known as c.211A>T), located in coding exon 2 of the RAD51C gene, results from an A to T substitution at nucleotide position 211. The asparagine at codon 71 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae	RCV000535484	SCV000650008	uncertain significance	Fanconi anemia complementation group O	2023-11-11	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 71 of the RAD51C protein (p.Asn71Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 232705). 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.
Color Diagnostics, LLC DBA Color Health	RCV000220314	SCV000686333	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-09	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with tyrosine at codon 71 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual with suspected Lynch Syndrome in the literature (PMID: 25980754). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sema4, Sema4	RCV000220314	SCV002531804	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-05	criteria provided, single submitter	curation
Fulgent Genetics, Fulgent Genetics	RCV002485426	SCV002801492	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2022-04-02	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002485426	SCV003920374	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2022-10-05	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature and is not present in large control databases. This variant is present in ClinVar (Variation ID: 232705). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.