ClinVar Miner

Submissions for variant NM_000232.5(SGCB):c.621+1G>T

gnomAD frequency: 0.00001  dbSNP: rs1264362642
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669104 SCV000793809 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2017-08-31 criteria provided, single submitter clinical testing
Invitae RCV000669104 SCV001390545 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-03-17 criteria provided, single submitter clinical testing Disruption of this splice site has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change affects a donor splice site in intron 4 of the SGCB gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SGCB are known to be pathogenic (PMID: 15938573, 18285821). ClinVar contains an entry for this variant (Variation ID: 553619). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.
Neuberg Centre For Genomic Medicine, NCGM RCV000669104 SCV004101525 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E criteria provided, single submitter clinical testing The splice site c.621+1G>T variant in SGCB gene has been reported previously in homozygous state in individuals affected with Muscular dystrophy, limbgirdle, autosomal recessive 4 (Balci B et al.). This variant has been submitted allele frequency 0.0008% in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar with varying interpretations: Pathogenic/ Likely Pathogenic. This sequence change affects a donor splice site in intron 4 of the SGCB gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants typically lead to a loss of protein function (Baralle D, Baralle M), and loss-of-function variants in SGCB are known to be pathogenic (Trabelsi M et al). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000669104 SCV004208732 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2E 2023-10-24 criteria provided, single submitter clinical testing

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