Submissions for variant NM_001080467.3(MYO5B):c.4240G>A (p.Glu1414Lys)

gnomAD frequency: 0.00039  dbSNP: rs76213287

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000730235	SCV000857960	uncertain significance	not provided	2018-04-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001126388	SCV001285578	uncertain significance	Congenital microvillous atrophy	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000730235	SCV001491652	uncertain significance	not provided	2024-12-04	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1414 of the MYO5B protein (p.Glu1414Lys). This variant is present in population databases (rs76213287, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MYO5B-related conditions. ClinVar contains an entry for this variant (Variation ID: 594845). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYO5B protein function with a negative predictive value of 80%. 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.
3billion, Medical Genetics	RCV004723143	SCV005328642	likely benign	Congenital microvillous atrophy; Cholestasis, progressive familial intrahepatic, 10	2024-09-20	criteria provided, single submitter	clinical testing	The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant.
PreventionGenetics, part of Exact Sciences	RCV003908037	SCV004721490	uncertain significance	MYO5B-related disorder	2024-04-26	no assertion criteria provided	clinical testing	The MYO5B c.4240G>A variant is predicted to result in the amino acid substitution p.Glu1414Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.072% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-47376012-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.