Submissions for variant NM_001130987.2(DYSF):c.2020A>G (p.Lys674Glu)

gnomAD frequency: 0.00050  dbSNP: rs139754493

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000487642	SCV000338018	uncertain significance	not provided	2015-12-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000292466	SCV000431745	uncertain significance	Miyoshi myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000328757	SCV000431746	uncertain significance	Limb-Girdle Muscular Dystrophy, Recessive	2016-06-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000487642	SCV000575214	uncertain significance	not provided	2021-12-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000487642	SCV000581854	likely benign	not provided	2018-12-06	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Reported in published literature (Pavoni et al., 2011) as 1966 A>G; K656Q,due to the use of alternate nomenclature, in individual with Miyoshi myopathy who also harbored the c.2200_2205delinsT; the phase of these variants is unknown; This variant is associated with the following publications: (PMID: 22046204, 21522182)
Athena Diagnostics Inc	RCV000487642	SCV000613188	uncertain significance	not provided	2021-08-03	criteria provided, single submitter	clinical testing
Invitae	RCV001085988	SCV000649620	likely benign	Qualitative or quantitative defects of dysferlin	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001085988	SCV001300090	uncertain significance	Qualitative or quantitative defects of dysferlin	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.
Genome-Nilou Lab	RCV001563948	SCV001787013	uncertain significance	Miyoshi muscular dystrophy 1	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001563949	SCV001787014	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001563950	SCV001787015	uncertain significance	Distal myopathy with anterior tibial onset	2021-07-14	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000487642	SCV003829643	uncertain significance	not provided	2022-09-19	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003416078	SCV004113488	uncertain significance	DYSF-related condition	2023-03-21	criteria provided, single submitter	clinical testing	The DYSF c.1966A>G variant is predicted to result in the amino acid substitution p.Lys656Glu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.31% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, including 1 homozygote (http://gnomad.broadinstitute.org/variant/2-71780972-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.