Submissions for variant NM_000337.6(SGCD):c.700-19T>C

gnomAD frequency: 0.02231  dbSNP: rs80086857

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000243653	SCV000303690	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000243653	SCV000700499	benign	not specified	2017-02-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000243653	SCV001363523	benign	not specified	2019-11-18	criteria provided, single submitter	clinical testing	Variant summary: SGCD c.700-19T>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.005 in 248096 control chromosomes, predominantly at a frequency of 0.068 within the African or African-American subpopulation in the gnomAD database, including 39 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2720-fold the estimated maximal pathogenic allele frequency expected for a variant in SGCD causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.700-19T>C in individuals affected with Cardiomyopathy and no experimental evidence demonstrating an impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001618380	SCV001477897	benign	not provided	2022-09-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001618380	SCV001844218	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002057343	SCV002422768	benign	Autosomal recessive limb-girdle muscular dystrophy type 2F	2025-02-04	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002057343	SCV003931903	benign	Autosomal recessive limb-girdle muscular dystrophy type 2F	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003233517	SCV003931904	benign	Dilated cardiomyopathy 1L	2023-02-08	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000243653	SCV001921219	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000243653	SCV001929985	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000243653	SCV001973676	benign	not specified		no assertion criteria provided	clinical testing