Submissions for variant NM_020975.6(RET):c.1828A>C (p.Asn610His)

dbSNP: rs1837994023

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001305413	SCV001494748	uncertain significance	Multiple endocrine neoplasia, type 2	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 610 of the RET protein (p.Asn610His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 1008125). 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.
Ambry Genetics	RCV002411977	SCV002711124	uncertain significance	Hereditary cancer-predisposing syndrome	2024-11-25	criteria provided, single submitter	clinical testing	The c.1828A>C (p.N610H) alteration is located in exon 10 (coding exon 10) of the RET gene. This alteration results from a A to C substitution at nucleotide position 1828, causing the asparagine (N) at amino acid position 610 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV001305413	SCV004824665	uncertain significance	Multiple endocrine neoplasia, type 2	2023-05-04	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with histidine at codon 610 of the RET 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 not been reported in individuals affected with RET-related disorders in the literature. 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.
GenomeConnect - Invitae Patient Insights Network	RCV001535690	SCV001749766	not provided	Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Multiple endocrine neoplasia type 2A		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 07-24-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
GenomeConnect, ClinGen	RCV001824949	SCV002074996	not provided	Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2A		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 07-24-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.