ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.13621T>A (p.Leu4541Met)

gnomAD frequency: 0.00003  dbSNP: rs769260277
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844664 SCV002103871 uncertain significance not specified 2022-02-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002543324 SCV003454038 likely benign Spastic paraplegia 2024-02-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV003163995 SCV003904435 uncertain significance Inborn genetic diseases 2023-03-01 criteria provided, single submitter clinical testing The c.13621T>A (p.L4541M) alteration is located in exon 10 (coding exon 9) of the SACS gene. This alteration results from a T to A substitution at nucleotide position 13621, causing the leucine (L) at amino acid position 4541 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Neuberg Centre For Genomic Medicine, NCGM RCV003339758 SCV004047554 uncertain significance Charlevoix-Saguenay spastic ataxia criteria provided, single submitter clinical testing The missense variant c.13621T>A (p.Leu4541Met) in SACS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Leu4541Met variant has allele frequency 0.002% in gnomAD exomes and novel (not in any individuals) in 1000 Genomes. This variant has reported to the ClinVar database as Uncertain Significance. The amino acid Leu at position 4541 is changed to a Met changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Leu4541Met in SACS is predicted as conserved by PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance (VUS).

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