Submissions for variant NM_000179.3(MSH6):c.3316GAT[1] (p.Asp1107del)

dbSNP: rs1064795429

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486507	SCV000571220	uncertain significance	not provided	2021-03-10	criteria provided, single submitter	clinical testing	In-frame deletion of 1 amino acid in a non-repeat region; Not observed at a significant frequency in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports a deleterious effect on protein structure/function
Invitae	RCV000530102	SCV000624845	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2023-12-08	criteria provided, single submitter	clinical testing	This variant, c.3319_3321del, results in the deletion of 1 amino acid(s) of the MSH6 protein (p.Asp1107del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 421891). 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.
Color Diagnostics, LLC DBA Color Health	RCV000580608	SCV000685389	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-05	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of one amino acid located in the ATPase domain in exon 5 of the MSH6 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/251414 chromosomes 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.
Ambry Genetics	RCV000580608	SCV001181350	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-24	criteria provided, single submitter	clinical testing	The c.3319_3321delGAT variant (also known as p.D1107del) is located in coding exon 5 of the MSH6 gene. This variant results from an in-frame GAT deletion at nucleotide positions 3319 to 3321. This results in the in-frame deletion of an aspartic acid at codon 1107. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV004003364	SCV004835046	uncertain significance	Lynch syndrome	2023-06-15	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of one amino acid located in the ATPase domain in exon 5 of the MSH6 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has been identified in 1/251414 chromosomes 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.