Submissions for variant NM_001077365.2(POMT1):c.1727T>C (p.Val576Ala)

gnomAD frequency: 0.00016  dbSNP: rs144338642

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000246533	SCV000311743	likely benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000725940	SCV000340670	uncertain significance	not provided	2016-03-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000332912	SCV000477671	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K	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.
Invitae	RCV000687622	SCV000815201	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2022-09-13	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 598 of the POMT1 protein (p.Val598Ala). This variant is present in population databases (rs144338642, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 260143). 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 POMT1 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.
GeneDx	RCV000725940	SCV001770984	uncertain significance	not provided	2019-05-14	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002518638	SCV003707542	uncertain significance	Inborn genetic diseases	2021-06-29	criteria provided, single submitter	clinical testing	The c.1793T>C (p.V598A) alteration is located in exon 18 (coding exon 17) of the POMT1 gene. This alteration results from a T to C substitution at nucleotide position 1793, causing the valine (V) at amino acid position 598 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.