Submissions for variant NM_013382.7(POMT2):c.1250A>G (p.Lys417Arg)

gnomAD frequency: 0.00011  dbSNP: rs147268052

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000249376	SCV000311978	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000658700	SCV000568954	uncertain significance	not provided	2022-11-30	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000524642	SCV000649917	uncertain significance	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2; Autosomal recessive limb-girdle muscular dystrophy type 2N	2022-10-08	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 417 of the POMT2 protein (p.Lys417Arg). This variant is present in population databases (rs147268052, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with POMT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 260291). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POMT2 protein function. 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.
CeGaT Center for Human Genetics Tuebingen	RCV000658700	SCV000780486	uncertain significance	not provided	2018-01-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001116051	SCV001274075	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2N	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Revvity Omics, Revvity	RCV000658700	SCV003809752	uncertain significance	not provided	2021-04-16	criteria provided, single submitter	clinical testing