ClinVar Miner

Submissions for variant NM_001142649.2(ANO5):c.986dup (p.Leu329fs) (rs398124626)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000082856 SCV000225111 pathogenic not provided 2015-09-18 criteria provided, single submitter clinical testing The c.989dupT ANO5 pathogenic variant has been reported in an individual with LGMD2L 1 and is of a type expected to cause disease. 1. Sarkozy et al. Hum Mutat. 2013 Aug;34(8):1111-8. AMK 5-13-16
Athena Diagnostics Inc RCV000173931 SCV000255646 pathogenic Limb-girdle muscular dystrophy, type 2L 2015-04-14 criteria provided, single submitter clinical testing
GeneDx RCV000082856 SCV000329067 pathogenic not provided 2018-04-11 criteria provided, single submitter clinical testing The c.989dupT variant in the ANO5 gene has been reported previously in the compound heterozygous state along with another ANO5 pathogenic variant in multiple individuals with limb-girdle muscular dystrophy type 2L, also known as anoctaminopathy (Sarkozy et al., 2013; Blackburn at al., 2017; Levesque et al., 2016). The c.989dupT variant is not observed in large population cohorts (Lek et al., 2016). The c.989dupT pathogenic variant causes a frameshift starting with codon Leucine 330, changes this amino acid to a Phenylalanine residue and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Leu330PhefsX6. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, c.989dupT is considered a pathogenic variant.
Invitae RCV000697761 SCV000826389 pathogenic Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L 2019-05-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu330Phefs*6) in the ANO5 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs754537193, ExAC 0.02%). This variant has been observed in several individuals affected with limb-girdle muscular dystrophy (PMID: 27862037, 23606453). In one of these individuals, it was observed on the opposite chromosome (in trans) from a pathogenic variant (PMID: 27862037). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 96688). Loss-of-function variants in ANO5 are known to be pathogenic (PMID: 21186264, 23606453, 25891276). For these reasons, this variant has been classified as Pathogenic.
GenomeConnect, ClinGen RCV000509090 SCV000607144 not provided Gnathodiaphyseal dysplasia; Limb-girdle muscular dystrophy, type 2L; Miyoshi muscular dystrophy 3 no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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