Submissions for variant NM_001130987.2(DYSF):c.5333C>A (p.Pro1778Gln)

gnomAD frequency: 0.00033  dbSNP: rs145272777

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000374736	SCV000338824	uncertain significance	not provided	2017-04-04	criteria provided, single submitter	clinical testing
Counsyl	RCV000664874	SCV000788897	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2017-01-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000374736	SCV000892569	uncertain significance	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000778917	SCV000915327	uncertain significance	Qualitative or quantitative defects of dysferlin	2018-02-13	criteria provided, single submitter	clinical testing	The DYSF gene is the only gene in which variants are known to cause dysferlinopathy. The DYSF c.5216C>A (p.Pro1739Gln) missense variant has been reported in one study in which it is found in two siblings from a family with a history of dysferlinopathy. The variant was found in a compound heterozygous state with a deletion in one sibling and in a heterozygous state in the other (Jin et al. 2016). Both siblings were found to be negative for dysferlin expression using immunohistochemical analysis of muscle tissue (Jin et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.005924 in the Ashkenazi Jewish population of the Genome Aggregation Database. Based on the evidence, the p.Pro1739Gln variant is classified as a variant of unknown significance but suspicious for pathogenicity for dysferlinopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000778917	SCV001018414	likely benign	Qualitative or quantitative defects of dysferlin	2024-01-20	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001329706	SCV001521220	uncertain significance	Miyoshi muscular dystrophy 1	2019-03-28	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab	RCV001329706	SCV001786745	uncertain significance	Miyoshi muscular dystrophy 1	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000664874	SCV001786746	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2021-07-14	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001563739	SCV001786747	uncertain significance	Distal myopathy with anterior tibial onset	2021-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000374736	SCV001788468	likely benign	not provided	2020-09-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30564623, 27647186)
Natera, Inc.	RCV000664874	SCV001463473	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-01-06	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003940011	SCV004752780	likely benign	DYSF-related disorder	2019-12-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).